US20050239897A1 - Mesenchymal stem cells and uses therefor - Google Patents

Mesenchymal stem cells and uses therefor Download PDF

Info

Publication number
US20050239897A1
US20050239897A1 US11/080,298 US8029805A US2005239897A1 US 20050239897 A1 US20050239897 A1 US 20050239897A1 US 8029805 A US8029805 A US 8029805A US 2005239897 A1 US2005239897 A1 US 2005239897A1
Authority
US
United States
Prior art keywords
animal
cells
mesenchymal stem
stem cells
mscs
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/080,298
Other languages
English (en)
Inventor
Mark Pittenger
Sudeepta Aggarwal
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
OSINIS THERAPEUTICS Inc
Mesoblast International SARL
Original Assignee
OSINIS THERAPEUTICS Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=39772836&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20050239897(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by OSINIS THERAPEUTICS Inc filed Critical OSINIS THERAPEUTICS Inc
Priority to US11/080,298 priority Critical patent/US20050239897A1/en
Assigned to OSINIS THERAPEUTICS, INC. reassignment OSINIS THERAPEUTICS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: AGGARWAL, SUDEEPTA, PITTENGER, MARK F.
Publication of US20050239897A1 publication Critical patent/US20050239897A1/en
Assigned to NAVY, UNITED STATES OF AMERICA, THE, AS REPRESENTED BY THE SECRETARY reassignment NAVY, UNITED STATES OF AMERICA, THE, AS REPRESENTED BY THE SECRETARY CONFIRMATORY LICENSE (SEE DOCUMENT FOR DETAILS). Assignors: OSIRIS THERAPEUTICS, INC.
Assigned to NAVY, SECRETARY OF THE UNITED STATES reassignment NAVY, SECRETARY OF THE UNITED STATES CONFIRMATORY LICENSE (SEE DOCUMENT FOR DETAILS). Assignors: OSIRIS THERAPEUTICS, INC.
Priority to US11/541,853 priority patent/US20080213227A1/en
Priority to US11/726,676 priority patent/US20080095749A1/en
Priority to US12/091,370 priority patent/US20090220464A1/en
Priority to US12/323,129 priority patent/US20090180997A1/en
Priority to US12/727,971 priority patent/US20100172885A1/en
Priority to US12/868,415 priority patent/US20100330048A1/en
Priority to US12/908,119 priority patent/US20110027238A1/en
Priority to US12/974,125 priority patent/US20110142807A1/en
Priority to US13/222,778 priority patent/US20110318314A1/en
Priority to US13/222,831 priority patent/US20110318315A1/en
Priority to US13/222,701 priority patent/US20110311496A1/en
Assigned to MESOBLAST INTERNATIONAL SÀRL reassignment MESOBLAST INTERNATIONAL SÀRL ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: OSIRIS THERAPEUTICS, INC.
Priority to US14/087,830 priority patent/US9943547B2/en
Priority to US14/138,577 priority patent/US10668101B2/en
Priority to US14/305,240 priority patent/US20140328807A1/en
Priority to US14/334,128 priority patent/US9694035B2/en
Priority to US14/739,924 priority patent/US20150272997A1/en
Priority to US16/204,936 priority patent/US10729727B2/en
Priority to US16/206,235 priority patent/US10716814B2/en
Priority to US16/214,485 priority patent/US11389484B2/en
Priority to US16/811,900 priority patent/US10960025B2/en
Priority to US16/815,784 priority patent/US10828334B1/en
Priority to US17/836,786 priority patent/US20230076630A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2026—IL-4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2066—IL-10
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0663—Bone marrow mesenchymal stem cells (BM-MSC)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0664—Dental pulp stem cells, Dental follicle stem cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0665—Blood-borne mesenchymal stem cells, e.g. from umbilical cord blood
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0666—Mesenchymal stem cells from hair follicles
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0667—Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0668—Mesenchymal stem cells from other natural sources
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • This invention relates to mesenchymal stem cells. More particularly, this invention relates to novel uses for mesenchymal stem cells, including promoting angiogenesis in various tissues and organs, treating autoimmune diseases, treating allergic responses, treating cancer, treating inflammatory diseases and disorders, and promoting would healing.
  • MSCs Mesenchymal stem cells
  • MSCs have been shown to provide effective feeder layers for expansion of hematopoietic and embryonic stem cells (Eaves, et al., Ann. N.Y. Acad. Sci., Vol. 938, pg.
  • MSCs may be useful in the repair or regeneration of damaged bone, cartilage, meniscus or myocardial tissues (DeKok, et al., Clin. Oral Implants Res., Vol. 14, pg. 481 (2003)); Wu, et al., Transplantation, Vol. 75, pg. 679 (2003); Noel, et al., Curr. Opin. Investig. Drugs, Vol. 3, pg. 1000 (2002); Ballas, et al., J. Cell. Biochem. Suppl., Vol. 38, pg.
  • MSCs express major histocompatibility complex (MHC) class I antigen on their surface but limited MHC class II (Le Blanc, et al., Exp. Hematol., Vol. 31, pg. 890 (2003); Potian, et al., J. Immunol., Vol. 171, pg. 3426 (2003)) and no B7 or CD40 co-stimulatory molecules (Majumdar, et al., J. Biomed. Sci., Vol. 10, pg. 228 (2003)), suggesting that these cells have a low-immunogenic phenotype (Tse, et al., Transplantation, Vol. 75, pg. 389 (2003)).
  • MHC major histocompatibility complex
  • MSCs also inhibit T-cell proliferative responses in an MHC-independent manner (Bartholomew, et al., Exp. Hematol., Vol. 30, pg. 42 (2002); Devine, et al., Cancer J., Vol. 7, pg. 576 (2001); DiNicola, et al., Blood, Vol. 99, pg. 3838 (2002)).
  • These immunological properties of MSCs may enhance their transplant engraftment and limit the ability of the recipient immune system to recognize and reject allogeneic cells following transplantation.
  • MSCs that modulate the immune response and support hematopoiesis together with their ability to differentiate into appropriate cell types under local stimuli make them desirable stem cells for cellular transplantation studies (Majumdar, et al., Hematother. Stem Cell Res., Vol. 9, pg. 841 (2000); Haynesworth, et al., J. Cell. Physiol., Vol. 166, pg. 585 (1996).
  • mesenchymal stem cells may regulate the production of various factors that may regulate several steps in the immune response process.
  • the mesenchymal stem cells may be employed in the treatment of disease conditions and disorders involving the immune system, or diseases, conditions, or disorders involving inflammation or allergic responses.
  • Such diseases, conditions, and disorders include, but are not limited to, autoimmune diseases, allergies, arthritis, inflamed wounds, alopecia araeta (baldness), periodontal diseases including gingivitis and periodontitis, and other diseases, conditions or disorders involving an immune response.
  • PBMCs peripheral blood mononuclear cells
  • VEGF vascular endothelial growth factor
  • mesenchymal stem cells stimulate dendritic cells (DCs) to produce Interferon-Beta (IFN- ⁇ ), which promotes tumor suppression and immunity against viral infection.
  • DCs dendritic cells
  • IFN- ⁇ Interferon-Beta
  • a method of treating an autoimmune disease in an animal comprises administering to the animal mesenchymal stem cells in an amount effective to treat the autoimmune disease in the animal.
  • IL-10 Interleukin-10
  • T reg cells regulatory T-cells
  • DC dendritic cells
  • Autoimmune diseases which may be treated in accordance with the present invention include, but are not limited to, multiple sclerosis, Type 1 diabetes, rheumatoid arthritis, uveitis, autoimmune thyroid disease, inflammatory bowel disease, autoimmune lymphoproliferative disease (ALPS), demyelinating disease, autoimmune encephalomyelitis, autoimmune gastritis (AIG), and autoimmune glomerular diseases. It is to be understood, however, that the scope of the present invention is not to be limited to the treatment of the specific autoimmune diseases mentioned herein.
  • the animal to which the mesenchymal stem cells are administered is a mammal.
  • the mammal may be a primate, including human and non-human primates.
  • the mesenchymal stem cell (MSC) therapy is based, for example, on the following sequence: harvest of MSC-containing tissue, isolation and expansion of MSCs, and administration of the MSCs to the animal, with or without biochemical or genetic manipulation.
  • the mesenchymal stem cells that are administered may be a homogeneous composition or may be a mixed cell population enriched in MSCs.
  • Homogeneous mesenchymal stem cell compositions may be obtained by culturing adherent marrow or periosteal cells, and the mesenchymal stem cell compositions may be obtained by culturing adherent marrow or periosteal cells, and the mesenchymal stem cells may be identified by specific cell surface markers which are identified with unique monoclonal antibodies.
  • a method for obtaining a cell population enriched in mesenchymal stem cells is described, for example, in U.S. Pat. No. 5,486,359.
  • Alternative sources for mesenchymal stem cells include, but are not limited to, blood, skin, cord blood, muscle, fat, bone, and perichondrium.
  • the mesenchymal stem cells may be administered by a variety of procedures.
  • the mesenchymal stem cells may be administered systemically, such as by intravenous, intraarterial, or intraperitoneal administration.
  • the mesenchymal stem cells may be from a spectrum of sources including autologous, allogeneic, or xenogeneic.
  • the mesenchymal stem cells are administered in an amount effective to treat an autoimmune disease in an animal.
  • the mesenchymal stem cells may be administered in an amount of from about 1 ⁇ 10 5 cells/kg to about 1 ⁇ 10 7 cells/kg, preferably from about 1 ⁇ 10 6 cells/kg to about 5 ⁇ 10 6 cells/kg.
  • the amount of mesenchymal stem cells to be administered is dependent upon a variety of factors, including the age, weight, and sex of the patient, the autoimmune disease to be treated, and the extent and severity thereof.
  • the mesenchymal stem cells may be administered in conjunction with an acceptable pharmaceutical carrier.
  • the mesenchymal stem cells may be administered as a cell suspension in a pharmaceutically acceptable liquid medium for injection.
  • a method of treating an inflammatory response in an animal comprises administering to the animal mesenchymal stem cells in an amount effective to treat the inflammatory response in the animal.
  • the mesenchymal stem cells promote T-cell maturation to regulatory T-cells (T reg ), thereby controlling inflammatory responses. It is also believed that the mesenchymal stem cells inhibit T helper 1 cells (Th1 cells), thereby decreasing the expression of the Interferon- ⁇ (IFN- ⁇ ) in certain inflammatory reactions, such as those associated with psoriasis, for example.
  • T reg regulatory T-cells
  • IFN- ⁇ Interferon- ⁇
  • the inflammatory responses which may be treated are those associated with psoriasis.
  • the mesenchymal stem cells may be administered to an animal such that the mesenchymal stem cells contact microglia and/or astrocytes in the brain to reduce inflammation, whereby the mesenchymal stem cells limit neurodegeneration caused by activated glial cells in diseases or disorders such as Alzheimer's Disease, Parkinson's Disease, stroke, or brain cell injuries.
  • the mesenchymal stem cells may be administered to an animal such that the mesenchymal stem cells contact keratinocytes and Langerhans cells in the epidermis of the skin to reduce inflammation as may occur in psoriasis, chronic dermatitis, and contact dermatitis.
  • this embodiment is not to be limited to any theoretical reasoning, it is believed that the mesenchymal stem cells may contact the keratinocytes and Langerhans cells in the epidermis, and alter the expression of T-cell receptors and cytokine secretion profiles, leading to decreased expression of tumor necrosis factor-alpha (TNF- ⁇ ) and increased regulatory T-cell (Treg cell) population.
  • TNF- ⁇ tumor necrosis factor-alpha
  • Treg cell regulatory T-cell
  • the mesenchymal stem cells may be used to reduce inflammation in the bone, as occurs in arthritis and arthritis-like conditions, including but not limited to, osteoarthritis and rheumatoid arthritis, and other arthritic diseases listed in the website www.arthritis.org/conditions/diseases.
  • arthritis and arthritis-like conditions including but not limited to, osteoarthritis and rheumatoid arthritis, and other arthritic diseases listed in the website www.arthritis.org/conditions/diseases.
  • the mesenchymal stem cells may be used to limit inflammation in the gut and liver during inflammatory bowel disease and chronic hepatitis, respectively.
  • the scope of this aspect of the present invention is not intended to be limited to any theoretical reasoning, it is believed that the mesenchymal stem cells promote increased secretion of Interleukin-10 (IL-10) and the generation of regulatory T-cells (Treg cells).
  • IL-10 Interleukin-10
  • Treg cells regulatory T-cells
  • the mesenchymal stem cells may be used to inhibit excessive neutrophil and macrophage activation in pathological conditions such as sepsis and trauma, including burn injury, surgery, and transplants.
  • pathological conditions such as sepsis and trauma, including burn injury, surgery, and transplants.
  • the mesenchymal stem cells promote secretion of suppressive cytokines such as IL-10, and inhibit macrophage migration inhibitory factor.
  • the mesenchymal stem cells may be used to control inflammation in immune privileged sites such as the eye, including the cornea, lens, pigment epithelium, and retina, brain, spinal cord, pregnant uterus and placenta, ovary, testes, adrenal cortex, liver, and hair follicles.
  • immune privileged sites such as the eye, including the cornea, lens, pigment epithelium, and retina, brain, spinal cord, pregnant uterus and placenta, ovary, testes, adrenal cortex, liver, and hair follicles.
  • the mesenchymal stem cells may be used to control end-stage renal disease (ESRD) infections during dialysis and/or glomerulonephritis.
  • ESRD end-stage renal disease
  • mesenchymal stem cells induce peripheral blood mononuclear cells to express vascular endothelial growth factor, or VEGF, which stimulates glomerular structuring.
  • VEGF vascular endothelial growth factor
  • the mesenchymal stem cells may be used to control viral infections such as influenza, hepatitis C, Herpes Simplex Virus, vaccinia virus infections, and Epstein-Barr virus.
  • viral infections such as influenza, hepatitis C, Herpes Simplex Virus, vaccinia virus infections, and Epstein-Barr virus.
  • IFN- ⁇ Interferon-Beta
  • the mesenchymal stem cells may be used to control parasitic infections such as Leishmania infections and Helicobacter infections.
  • parasitic infections such as Leishmania infections and Helicobacter infections.
  • Th2 T helper 2
  • IgE Immunoglobulin E
  • the mesenchymal stem cells may be administered to a mammal, including human and non-human primates, as hereinabove described.
  • the mesenchymal stem cells also may be administered systemically, as hereinabove described.
  • the mesenchymal stem cells may be administered directly to an arthritic joint.
  • the mesenchymal stem cells are administered in an amount effective to treat an inflammatory response in an animal.
  • the mesenchymal stem cells may be administered in an amount of from about 1 ⁇ 10 5 cells/kg to about 1 ⁇ 10 7 cells/kg, preferably from about 1 ⁇ 10 6 cells/kg to about 5 ⁇ 10 6 cells/kg.
  • the exact dosage of mesenchymal stem cells to be administered is dependent upon a variety of factors, including the age, weight, and sex of the patient, the inflammatory response being treated, and the extent and severity thereof.
  • the mesenchymal stem cells may be administered in conjunction with an acceptable pharmaceutical carrier, as hereinabove described.
  • a method of treating cancer in an animal comprises administering to the animal mesenchymal stem cells in an amount effective to treat cancer in the animal.
  • the scope of this aspect of the present invention is not to be limited to any theoretical reasoning, it is believed that the mesenchymal stem cells interact with dendritic cells, which leads to IFN- ⁇ secretion, which in turn acts as a tumor suppressor.
  • Cancers which may be treated include, but are not limited to, hepatocellular carcinoma, cervical cancer, pancreatic cancer, prostate cancer, fibrosarcoma, medullablastoma, and astrocytoma. It is to be understood, however, that the scope of the present invention is not to be limited to any specific type of cancer.
  • the animal may be a mammal, including human and non-human primates, as hereinabove described.
  • the mesenchymal stem cells are administered to the animal in an amount effective to treat cancer in the animal.
  • the mesenchymal stem cells are administered in an amount of from about 1 ⁇ 10 5 cells/kg to about 1 ⁇ 10 7 cells/kg, preferably from about 1 ⁇ 10 6 cells/kg to about 5 ⁇ 10 6 cells/kg.
  • the exact amount of mesenchymal stem cells to be administered is dependent upon a variety of factors, including the age, weight, and sex of the patient, the type of cancer being treated, and the extent and severity thereof.
  • the mesenchymal stem cells are administered in conjunction with an acceptable pharmaceutical carrier, and may be administered sytemically, as hereinabove described. Alternatively, the mesenchymal stem cells may be administered directly to the cancer being treated.
  • a method of treating an allergic disease or disorder in an animal comprises administering to the animal mesenchymal stem cells in an amount effective to treat the allergic disease or disorder in the animal.
  • mesenchymal stem cells when administered after an acute allergic response, provide for inhibition of mast cell activation and degranulation. Also, it is believed that the mesenchymal, stem cells downregulate basophil activation and inhibit cytokines such as TNF- ⁇ , chemokines such as Interleukin-8 and monocyte chemoattractant protein, or MCP-1, lipid mediators such as leukotrienes, and inhibit main mediators such as histamine, heparin, chondroitin sulfates, and cathepsin.
  • cytokines such as TNF- ⁇
  • chemokines such as Interleukin-8 and monocyte chemoattractant protein, or MCP-1
  • lipid mediators such as leukotrienes
  • main mediators such as histamine, heparin, chondroitin sulfates, and cathepsin.
  • Allergic diseases or disorders which may be treated include, but are not limited to, asthma, allergic rhinitis, atopic dermatitis, and contact dermatitis. It is to be understood, however, that the scope of the present invention is not to be limited to any specific allergic disease or disorder
  • the mesenchymal stem cells are administered to the animal in an amount effective to treat the allergic disease or disorder in the animal.
  • the animal may be a mammal.
  • the mammal may be a primate, including human and non-human primates.
  • the mesenchymal stem cells are administered in an amount of from about 1 ⁇ 10 5 cells/kg to about 1 ⁇ 10 7 cells/kg, preferably from about 1 ⁇ 10 6 cells/kg to about 5 ⁇ 10 6 cells/kg.
  • the exact dosage is dependent upon a variety of factors, including the age, weight, and sex of the patient, the allergic disease or disorder being treated, and the extent and severity thereof.
  • the mesenchymal stem cells may be administered in conjunction with an acceptable pharmaceutical carrier, as hereinabove described.
  • the mesenchymal stem cells may be administered systemically, such as by intravenous or intraarterial administration, for example.
  • a method of promoting wound healing in an animal comprises administering to the animal mesenchymal stem cells in an amount effective to promote wound healing in the animal.
  • the mesenchymal stem cells cause T reg cells and dendritic cells to release Interleukin-10 (IL-10).
  • IL-10 Interleukin-10 limits or controls inflammation in a wound, thereby promoting healing of a wound.
  • the mesenchymal stem cells may promote wound healing and fracture healing by inducing secretion factors by other cell types.
  • the mesenchymal stem cells may induce prostaglandin E2 (PGE 2 )-mediated release of vascular endothelial growth factor (VEGF) by peripheral blood mononuclear cells (PBMCs), as well as PGE 2 -mediated release of growth hormone, insulin, insulin-like growth factor 1 (IGF-1) insulin-like growth factor binding protein-3 (IGFBP-3), and endothelin-1.
  • PGE 2 prostaglandin E2
  • IGF-1 insulin-like growth factor 1
  • IGFBP-3 insulin-like growth factor binding protein-3
  • the mesenchymal stem cells are administered to the animal in an amount effective to promote wound healing in the animal.
  • the animal may be a mammal, and the mammal may be a primate, including human and non-human primates.
  • the mesenchymal stem cells are administered in an amount of from about 1 ⁇ 10 5 cells/kg to about 1 ⁇ 10 7 cells/kg, preferably from about 1 ⁇ 10 6 cells/kg to about 5 ⁇ 10 6 cells/kg.
  • the exact amount of mesenchymal stem cells to be administered is dependent upon a variety of factors, including the age, weight, and sex of the patient, and the extent and severity of the wound being treated.
  • the mesenchymal stem cells may be administered in conjunction with an acceptable pharmaceutical carrier, as hereinabove described.
  • the mesenchymal stem cells may be administered systemically, as hereinabove described.
  • the mesenchymal stem cells may be administered directly to a wound, such as in a fluid on a dressing or reservoir containing the mesenchymal stem cells.
  • a method of treating or preventing fibrosis in an animal comprises administering to the animal mesenchymal stem cells in an amount effective to treat or prevent fibrosis in an animal.
  • the mesenchymal stem cells may be administered to the animal in order to treat or prevent any type of fibrosis in the animal, including, but not limited to, cirrhosis of the liver, fibrosis of the kidneys associated with end-stage renal disease, and fibrosis of the lungs. It is to be understood that the scope of the present invention is not to be limited to any specific type of fibrosis.
  • the mesenchymal stem cells are administered to the animal in an amount effective to treat or prevent fibrosis in the animal.
  • the animal may be a mammal, and the mammal may be a primate, including human and non-human primates.
  • the mesenchymal stem cells are administered in an amount of from about 1 ⁇ 10 5 cells/kg to about 1 ⁇ 10 7 cells/kg, preferably from about 1 ⁇ 10 6 cells/kg to about 5 ⁇ 10 6 cells/kg.
  • the exact amount of mesenchymal stem cells to be administered is dependent upon a variety of factors, including the age, weight, and sex of the patient, and the extent and severity of the fibrosis being treated or prevented.
  • the mesenchymal stem cells may be administered in conjunction with an acceptable pharmaceutical carrier, as hereinabove described.
  • the mesenchymal stem cells may be administered systemically, also as hereinabove described.
  • a method of promoting angiogenesis in an organ or tissue of an animal comprises administering to the animal mesenchymal stem cells in an amount effective to promote angiogenesis in an organ or tissue of the animal.
  • Angiogenesis is the formation of new blood vessels from a pre-existing microvascular bed.
  • angiogenesis may be used to treat coronary and peripheral artery insufficiency, and thus may be a noninvasive and curative approach to the treatment of coronary artery disease, ischemic heart disease, and peripheral artery disease.
  • Angiogenesis may play a role in the treatment of diseases and disorders in tissue and organs other than the heart, as well as in the development and/or maintenance of organs other than the heart.
  • Angiogenesis may provide a role in the treatment of internal and external wounds, as well as dermal ulcers.
  • Angiogenesis also plays a role in embryo implantation, and placental growth, as well as the development of the embryonic vasculature.
  • Angiogenesis also is essential for the coupling of cartilage resorption with bone formation, and is essential for correct growth plate morphogenesis.
  • angiogenesis is necessary for the successful engineering and maintenance of highly metabolic organs, such as the liver, where a dense vascular network is necessary to provide sufficient nutrient and gas transport.
  • the mesenchymal stem cells can be administered to the tissue or organ in need of angiogenesis by a variety of procedures.
  • the mesenchymal stem cells may be administered systemically, such as by intravenous, intraarterial, or intraperitoneal administration, or the mesenchymal stem cells may be administered directly to the tissue or organ in need of angiogenesis, such as by direct injection into the tissue or organ in need of angiogenesis.
  • the mesenchymal stem cells may be from a spectrum of sources including autologous, allogeneic, or xenogeneic.
  • PBMCs peripheral blood mononuclear cells
  • VEGF vascular endothelial growth factor
  • the animal is a mammal.
  • the mammal may be a primate, including human and non-human primates.
  • the mesenchymal stem cells may be employed in the treatment, alleviation, or prevention of any disease or disorder which can be alleviated, treated, or prevented through angiogenesis.
  • the mesenchymal stem cells may be administered to an animal to treat blocked arteries, including those in the extremities, i.e., arms, legs, hands, and feet, as well as the neck or in various organs.
  • the mesenchymal stem cells may be used to treat blocked arteries which supply the brain, thereby treating or preventing stroke.
  • the mesenchymal stem cells may be used to treat blood vessels in embryonic and post-natal corneas and may be used to provide glomerular structuring.
  • the mesenchymal stem cells may be employed in the treatment of wounds, both internal and external, as well as the treatment of dermal ulcers found in the feet, hands, legs or arms, including, but not limited to, dermal ulcers caused by diseases such as diabetes and sickle cell anemia.
  • the mesenchymal stem sells may be employed to promote embryo implantation and prevent miscarriage.
  • mesenchymal stem cells may be administered to an unborn animal, including humans, to promote the development of the vasculature in the unborn animal.
  • the mesenchymal stem cells may be administered to an animal, born or unborn, in order to promote cartilage resorption and bone formation, as well as promote correct growth plate morphogenesis.
  • the mesenchymal stem cells are administered in an amount effective in promoting angiogenesis in an animal.
  • the mesenchymal stem cells may be administered in an amount of from about 1 ⁇ 10 5 cells/kg to about 1 ⁇ 10 7 cells/kg, preferably from about 1 ⁇ 10 6 cells/kg to about 5 ⁇ 10 6 cells/kg.
  • the amount of mesenchymal stem cells to be administered is dependent upon a variety of factors, including the age, weight, and sex of the patient, the disease or disorder to be treated, alleviated, or prevented, and the extent and severity thereof.
  • the mesenchymal stem cells may be administered in conjunction with an acceptable pharmaceutical carrier.
  • the mesenchymal stem cells may be administered as a cell suspension in a pharmaceutically acceptable liquid medium for injection. Injection can be local, i.e., directly into the tissue or organ in need of angiogenesis, or systemic.
  • the mesenchymal stem cells may be genetically engineered with one or more polynucleotides encoding a therapeutic agent.
  • the polynucleotides may be delivered to the mesenchymal stem cells via an appropriate expression vehicle.
  • Expression vehicles which may be employed to genetically engineer the mesenchymal stem cells include, but are not limited to, retroviral vectors, adenoviral vectors, and adeno-associated virus vectors.
  • polynucleotide encoding a therapeutic agent is dependent upon various factors, including the disease or disorder being treated, and the extent and severity thereof. Polynucleotides encoding therapeutic agents, and appropriate expression vehicles are described further in U.S. Pat. No. 6,355,239.
  • mesenchymal stem cells when employed in the above-mentioned therapies and treatments, may be employed in combination with other therapeutic agents known to those skilled in the art, including, but not limited to, growth factors, cytokines, drugs such as anti-inflammatory drugs, and cells other than mesenchymal stem cells, such as dendritic cells, and may be administered with soluble carriers for cells such as hyalurionic acid, or in combination with solid matrices, such collagen, gelatin, or other biocompatible polymers, as appropriate.
  • growth factors including, but not limited to, growth factors, cytokines, drugs such as anti-inflammatory drugs, and cells other than mesenchymal stem cells, such as dendritic cells, and may be administered with soluble carriers for cells such as hyalurionic acid, or in combination with solid matrices, such collagen, gelatin, or other biocompatible polymers, as appropriate.
  • cytokines drugs
  • drugs such as anti-inflammatory drugs
  • cells other than mesenchymal stem cells such as dendritic
  • FIG. 1 MSCs modulate dendritic cell functions.
  • A Flow cytometric analysis of mature monocytic DC1 cells using antibodies against HLA-DR and CD11c and of plasmacytoid DC2 cells using antibodies against HLA-DR and CD123 (IL-3 receptor).
  • B MSCs inhibit TNF- ⁇ secretion (primary y-axis) and increase IL-10 secretion (secondary y-axis) from activated DC1 and DC2 respectively.
  • C MSCs cultured with mature DC1 cells inhibit IFN- ⁇ secretion (primary y-axis) by T cells and increase IL-4 levels (secondary y-axis) as compared to MSC or DC alone.
  • FIG. 2 MSCs inhibit pro-inflammatory effector T cell function.
  • A Flow cytometric analysis of T Reg cell numbers (in %) by staining PBMCs or non-adherent fraction in MSC+PBMC culture (MSC+PBMC) with FITC-conjugated CD4 (x-axis) and PE conjugated CD25 (y-axis) antibodies. Gates were set based on isotype control antibodies as background. Graphs are representative of 5 independent experiments.
  • B T H 1 cells generated in presence of MSCs secreted reduced levels of IFN- ⁇ (primary y-axis) and T H 2 cells generated in presence of MSCs secreted increased amounts of IL-4 (secondary y-axis) in cell culture supernatants.
  • C MSCs inhibit IFN- ⁇ secretion from purified NK cells cultured for 0, 24, or 48 hours in a 24-well plate. Data shown are mean ⁇ SD cytokine secretion in one experiment and are representative of 3 independent experiments.
  • FIG. 3 MSCs lead to increased numbers of T reg cell population and increased GITR expression.
  • MLR mixed lymphocyte reaction
  • PHA phytohemagglutinin
  • T reg population generated in the presence of MSCs was similar functionally to the T reg cells generated in the absence of MSCs (lane 2).
  • B PBMCs were cultured for 3 days in the absence (top plot) or presence (bottom plot) of MSCs (MSC to PBMC ratio 1:10), following which the non-adherent fraction was harvested and immunostained with FITC-labeled GITR and PE-labeled CD4. Results show a greater than twofold increase in GITR expression in cells cultured in the presence of MSCs.
  • FIG. 4 MSCs produce PGE 2 and blocking PGE 2 reverses MSC-mediated immuno-modulatory effects.
  • A PGE 2 secretion (mean ⁇ SD) in culture supernatants obtained from MSCs cultured in the presence or absence of PGE 2 blockers NS-398 or indomethacin (Indometh.) at various concentrations. Inhibitor concentrations are in ⁇ M and data presented are values obtained after 24 hour culture
  • B COX-1 and COX-2 expression in MSCs and PBMCs using real-time RT-PCR.
  • MSCs expressed significantly higher levels of COX-2 as compared to PBMCs, and when MSCs were cultured in presence of PBMCs, there was a >3-fold increase in COX-2 expression in MSCs. Representative data from 1 of 3 independent experiments is shown. The MSC+PBMC cultures were setup in a trans-well chamber plate where MSCs were plated onto the bottom chamber and PBMCs onto the top chamber.
  • C Presence of PGE 2 blockers indomethacin (Ind.) or NS-398 increases TNF- ⁇ secretion from activated DCs ( ⁇ ) and IFN- ⁇ secretion from T H 1 cells ( ) as compared to controls.
  • FIG. 5 Constituitive MSC cytokine secretion is elevated in the presence of allogeneic PBMCs.
  • cytokines IL-6 and VEGF, lipid mediator PGE 2 , and matrix metalloproteinase 1 (pro-MMP-1) were analyzed.
  • the MSCs produced IL-6, VEGF, and PGE 2 constituitively, and the levels of these factors increased upon co-culture with PBMCs, thereby suggesting that MSCs may play a role in modulating immune functions in an inflammatory setting.
  • FIG. 6 MSCs inhibit mitogen-induced T-cell proliferation in a dose-dependent manner.
  • Increasing numbers of allogeneic PBMCs were incubated with constant numbers of MSCs (2,000 cells/well) plated on a 96-well plate in the presence or absence of PHA (2.5 mg/ml) for 72 hours, and 3 H thymidine incorporation determined (in counts per minute, or cpm).
  • PHA 2.5 mg/ml
  • FIG. 7 Schematic diagram of proposed MSC mechanism of action
  • MSCs mediate their immuno-modulatory effects by affecting cells from both the innate (DCs-pathways 2-4; and NK-pathway 6) and adaptive (T-pathways 1 and 5 and B-pathway 7) immune systems.
  • immature DCs migrate to the site of potential entry, mature and acquire an ability to prime naive T cells (by means of antigen specific and co-stimulatory signals) to become protective effector T cells (cell-mediated T H 1 or humoral T H 2 immunity).
  • MSCs may alter the outcome of immune response by limiting the ability of DCs to mount a cell-mediated response (pathway 2) or by promoting the ability to mount a humoral response (pathway 4). Also, when mature effector T cells are present, MSCs may interact with them to skew the balance of T H 1 (pathway 1) responses towards T H 2 responses (pathway 5), and probably towards an increased IgE producing B cell activity (pathway 7), desirable outcomes for suppression of GvHD and autoimmune disease symptoms.
  • MSCs in their ability to result in an increased generation of T Reg population may result in a tolerant phenotype and may aid a recipient host by dampening bystander inflammation in their local micro-environment.
  • Dashed line (----) represents proposed mechanism.
  • MSCs Human MSCs were cultured as described by Pittenger et al., Science, Vol. 284, pg. 143 (1999). Briefly, marrow samples were collected from the iliac crest of anonymous donors following informed consent by Poietics Technologies, Div of Cambrex Biosciences. MSCs were cultured in complete Dulbecco's Modified Eagle's Medium-Low Glucose (Life Technologies, Carlsbad, Calif.) containing 1% antibiotic-antimyotic solution (Invitrogen, Carlsbad, Calif.) and 10% fetal bovine serum (FBS, JRH BioSciences, Lenexa, Kans.).
  • Dulbecco's Modified Eagle's Medium-Low Glucose Life Technologies, Carlsbad, Calif.
  • FBS fetal bovine serum
  • MSCs grew as an adherent monolayer and were detached with trypsin/EDTA (0.05% trypsin at 37° C. for 3 minutes). All MSCs used were previously characterized for multilineage potential and retained the capacity to differentiate into mesenchymal lineages (chondrocytic, adipogenic, and osteogenic) (Pittenger, et al., Science, Vol. 284, pg. 143 (1999)).
  • PBMCs Peripheral blood mononuclear cells
  • DCs dendritic cells
  • CD1c + monocytic lineage
  • CD1c expressing B cells were magnetically depleted of CD19 + cells using magnetic beads, followed by labeling the B-cell depleted fraction with biotin-labeled CD1c (BDCA1 + ) and anti-biotin antibodies and separating them from the unlabeled cell fraction utilizing magnetic columns according to the manufacturer's instructions (Miltenyi Biotech, Auburn, Calif.).
  • Precursors of DCs of plasmacytoid lineage were isolated from PBMCs by immuno-magnetic sorting of positively labeled antibody coated cells (BDCA2 + ) (Miltenyi Biotech, Auburn, Calif.).
  • MSCs and DCs were cultured in equal numbers for various time periods and cell culture supernatant collected and stored at ⁇ 80° C. until further evaluation.
  • MSCs were cultured with mature DC1 or DC2 cells (1:1 MSC:DC ratio) for 3 days, and then the combined cultures (MSCs and DCs) were irradiated to prevent any proliferation.
  • antibody purified, naive, allogeneic T cells (CD4 + ,CD45RA + ) were added to the irradiated MSCs/DCs and cultured for an additional 6 days.
  • the non-adherent cell fraction (purified T cells) was then collected from the cultures, washed twice and re-stimulated with PHA for another 24 hours, following which cell culture supernatants were harvested and analyzed for secreted IFN- ⁇ and IL-4 by ELISA.
  • NK cells Purified populations of NK cells were obtained by depleting non-NK cells that are magnetically labeled with a cocktail of biotin-conjugated monoclonal antibodies (anti-CD3, -CD14, -CD19, -CD36 and anti-IgE antibodies) as a primary reagent and anti-biotin monoclonal antibodies conjugated to Microbeads as secondary labeling reagent.
  • the magnetically labeled non-NK cells were retained in MACS (Miltenyi Biotech, Auburn, Calif.) columns in a magnetic field, while NK cells passed through and were collected.
  • the T Reg cell population was isolated using a 2-step isolation procedure.
  • First non-CD4 + T cells were indirectly magnetically labeled with a cocktail of biotin labeled antibodies and anti-biotin microbeads. The labeled cells were then depleted by separation over a MACS column (Miltenyi Biotech, Auburn, Calif.).
  • CD4 + CD25 + cells were directly labeled with CD25 microbeads and isolated by positive selection from the pre-enriched CD4 + T cell fraction.
  • the magnetically labeled CD4 + CD25 + T cells were retained on the column and eluted after removal of the column from the magnetic field.
  • CD4+CD25+ T reg cell populations were isolated from PBMC or MSC+PBMC (MSC to PBMC ratio 1:10) cultures (cultured without any further stimulation for 3 days) using a 2-step magnetic isolation procedure. These cells were irradiated to block any further proliferation and used as stimulators in a mixed lymphocyte reaction (MLR), where responders were allogeneic PBMCs (stimulator to responder ratio 1:100) in the presence of PHA (2.5 ⁇ g/ml). The culture was carried out for 48 hours, following which 3 H thymidine was added. Incorporated radioactivity was counted after 24 hours.
  • MLR mixed lymphocyte reaction
  • PBMCs were cultured in the absence or presence of MSCs (MSC to PBMC ratio 1:10), following which the non-adherent fraction was harvested and immunostained with FITC-labeled glucocorticoid-induced TNF receptor, or GITR, and PE-labeled CD4.
  • PBMCs Peripheral blood mononuclear cells
  • Non-adherent fraction was incubated in the presence of plate-bound anti-CD3 (5 ⁇ g/ml) and anti-CD28 (1 ⁇ g/ml) antibodies under T H 1 (IL-2 (4 ng/ml)+IL-12 (5 ng/ml)+anti-IL-4 (1 ⁇ g/ml)) or T H 2 (IL-2 (4 ng/ml)+IL-4 (4 ng/ml)+anti-IFN- ⁇ (1 ⁇ g/ml)) conditions for 3 days in the presence or absence of MSCs.
  • T H 1 IL-2 (4 ng/ml)+IL-12 (5 ng/ml)+anti-IL-4 (1 ⁇ g/ml)
  • T H 2 IL-2 (4 ng/ml)+IL-4 (4 ng/ml)+anti-IFN- ⁇ (1 ⁇ g/ml)
  • the cells were washed and then re-stimulated with PHA (2.5 ⁇ g/ml) for another 24 or 48 hours, following which levels of IFN- ⁇ and IL-4 were measured in culture supernatants by ELISA (R&D Systems, Minneapolis, Minn.).
  • IL-6 Interleukin-6
  • VEGF vascular endothelial growth factor
  • PGE 2 lipid mediator prostaglandin E 2
  • pro-MMP-1 matrix metalloproteinase 1
  • PBMCs Purified PBMCs were prepared by centrifuging leukopack (Cambrex, Walkersville, Md.) on Ficoll-Hypaque (Lymphoprep, Oslo, Norway). Separated cells were cultured (in triplicates) in the presence or absence of MSCs (plated 3-4 hours prior to PBMC addition to allow them to settle) for 48 hours in presence of the mitogen PHA (Sigma Chemicals, St. Louis, Mo.). In selected experiments, PBMCs were resuspended in medium containing PGE 2 inhibitors Indomethacin (Sigma Chemicals, St. Louis, Mo.) or NS-938 (Cayman Chemicals, Ann Arbor, Mich.).
  • RNA from cell pellets were prepared using a commercially available kit (Qiagen, Valencia, Calif.) and according to the manufacturer's instructions. Contaminating genomic DNA was removed using the DNA-free kit (Ambion, Austin, Tex.). Quantitative RT-PCR was performed on a MJ Research Opticon detection system (South San Francisco, Calif.) using QuantiTect SYBR Green RT-PCR kit (Qiagen, Valencia, Calif.) with primers at concentration of 0.5 ⁇ M. Relative changes in expression levels in cells cultured under different conditions were calculated by the difference in Ct values (crossing point) using ⁇ -actin as internal control.
  • COX-1 and COX-2 specific primers were: COX-1: 5′-CCG GAT GCC AGT CAG GAT GAT G-3′(forward), 5′-CTA GAC AGC CAG ATG CTG ACA G-3′ (reverse); COX-2: 5′-ATC TAC CCT CCT CM GTC CC-3′(forward), 5′-TAC CAG MG GGC AGG ATA CAG-3′ (reverse).
  • DC1 and DC2 precursor dendritic cells were isolated by immuno-magnetic sorting of BDCA1 + and BDCA2 + cells respectively and matured by incubation with GM-CSF and IL-4 (1 ⁇ 10 3 IU/ml and 1 ⁇ 10 3 IU/ml, respectively) for DC1 cells, or IL-3 (10 ng/ml) for DC2 cells.
  • GM-CSF and IL-4 (1 ⁇ 10 3 IU/ml and 1 ⁇ 10 3 IU/ml, respectively
  • IL-3 10 ng/ml
  • DC1 cells In the presence of the inflammatory agent bacterial lipopolysaccharide (LPS, 1 ng/ml), DC1 cells produced moderate levels of TNF- ⁇ but when MSCs were present (ratios examined 1:1 and 1:10), there was >50% reduction in TNF- ⁇ secretion ( FIG. 1B ).
  • DC2 cells produced IL-10 in the presence of LPS and its levels were increased greater than 2-fold upon MSC:DC2 co-culture (1:1) ( FIG. 1B ). Therefore, the MSCs modified the cytokine profile of activated DCs in culture towards a more tolerogenic phenotype.
  • activated DCs when cultured with MSCs, were able to reduce IFN- ⁇ and increase IL-4 levels secreted by naive CD4 + T cells ( FIG. 1C ) suggesting a MSC-mediated shift from pro-inflammatory to anti-inflammatory T cell phenotype.
  • T Reg T-regulatory cells
  • the CD4 + CD25 + T Reg cell population generated in presence of MSCs expressed increased levels of gluocorticoid-induced TNF receptor (GITR), a cell surface receptor expressed on T Reg cell populations, and was suppressive in nature as it suppressed allogeneic T cell proliferation ( FIG. 3A ,B).
  • MSCs were investigated as to their direct ability to affect T cell differentiation. Using antibody selected purified T cells (CD4 + Th cells), IFN- ⁇ producing T H 1 and IL-4 producing T H 2 cells were generated in presence or absence of MSCs. When MSCs were present during differentiation, there was reduced IFN- ⁇ secretion by T H 1 cells and increased IL-4 secretion by T H 2 cells ( FIG. 2B ).
  • MSCs modify T-cell functions by soluble factor(s) (LeBlanc, et al., Exp. Hematol., Vol. 31, pg. 890 (2003); Tse, et al., Transplantation, Vol. 75, pg. 389 (2003). It was observed that the MSCs secreted several factors, including IL-6, prostaglandin E 2 , VEGF and proMMP-1constitutively, and the levels of each increased upon culture with PBMCs ( FIG. 5 ).
  • MSCs were cultured with activated dendritic cells (DC1) or T H 1 cells in the presence of PGE 2 inhibitors NS-398 or indomethacin.
  • DC1s dendritic cells
  • NS-398 or indomethacin increased TNF- ⁇ secretion by DC1s, and IFN- ⁇ secretion from T H 1 cells ( FIG. 4C ), respectively, suggesting that MSC effects on immune cell types may be mediated by secreted PGE 2 .
  • Recent studies have shown that MSCs inhibit T-cell proliferation induced by various stimuli (DeNicola, et al., Blood, Vol. 99, pg.
  • MSCs inhibit mitogen-induced T cell proliferation in a dose-dependent manner ( FIG. 6 ) and when PGE 2 inhibitors NS-398 (5 ⁇ M) or indomethacin (4 ⁇ M) were present, there was a >70% increase in ( 3 H) thymidine incorporation by PHA-treated PBMCs in MSC containing cultures as compared to controls without inhibitors ( FIG. 4D ).
  • MSCs may interact with them directly and inhibit the pro-inflammatory IFN- ⁇ production (pathway 1) and promote regulatory T cell phenotype (pathway 3) and anti-inflammatory T H 2 cells (pathway 5). Further, MSCs can alter the outcome of the T cell immune response through DCs by secreting PGE 2 , inhibiting pro-inflammatory DC1 cells (pathway 2) and promoting anti-inflammatory DC2 cells (pathway 4) or regulatory DCs (pathway 3).
  • a shift towards T H 2 immunity suggests a change in B cell activity towards increased generation of IgE/IgG1 subtype antibodies (pathway 7).
  • MSCs by their ability to inhibit IFN- ⁇ secretion from NK cells likely modify NK cell function (pathway 6).
  • This model of MSC:Immune cell interactions is consistent with the experimentation performed in several other laboratories (LeBlanc, et al., Exp. Hematol., Vol. 31, pg. 890 (2003); Tse, et al., Transplantation, Vol. 75, pg. 389 (2003); DiNicola, et al., Blood, Vol. 99, pg. 3838 (2002)). Further examination of the proposed mechanisms is underway and animal studies are now necessary to examine the in vivo effects of MSC administration.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cell Biology (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Dermatology (AREA)
  • Virology (AREA)
  • Pulmonology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Endocrinology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Emergency Medicine (AREA)
  • Cardiology (AREA)
US11/080,298 2004-03-22 2005-03-15 Mesenchymal stem cells and uses therefor Abandoned US20050239897A1 (en)

Priority Applications (23)

Application Number Priority Date Filing Date Title
US11/080,298 US20050239897A1 (en) 2004-03-22 2005-03-15 Mesenchymal stem cells and uses therefor
US11/541,853 US20080213227A1 (en) 2004-03-22 2006-10-02 Mesenchymal stem cells and uses therefor
US11/726,676 US20080095749A1 (en) 2004-03-22 2007-03-22 Mesenchymal stem cells and uses therefor
US12/091,370 US20090220464A1 (en) 2004-03-22 2008-03-21 Mesenchymal stem cells and uses therefor
US12/323,129 US20090180997A1 (en) 2004-03-22 2008-11-25 Mesenchymal Stem Cells And Uses Therefor
US12/727,971 US20100172885A1 (en) 2004-03-22 2010-03-19 Multipotent Adult Stem Cells And Uses of Multipotent Adult Stem Cells To Treat Inflammation
US12/868,415 US20100330048A1 (en) 2004-03-22 2010-08-25 Mesenchymal stem cells and uses therefor
US12/908,119 US20110027238A1 (en) 2004-03-22 2010-10-20 Mesenchymal Stem Cells and Uses Therefor
US12/974,125 US20110142807A1 (en) 2004-03-22 2010-12-21 Mesenchymal Stem Cells and Uses Therefor
US13/222,701 US20110311496A1 (en) 2004-03-22 2011-08-31 Mesenchymal stem cells and uses therefor
US13/222,778 US20110318314A1 (en) 2004-03-22 2011-08-31 Mesenchymal stem cells and uses therefor
US13/222,831 US20110318315A1 (en) 2004-03-22 2011-08-31 Mesenchymal stem cells and uses therefor
US14/087,830 US9943547B2 (en) 2004-03-22 2013-11-22 Mesenchymal stem cells and uses therefor
US14/138,577 US10668101B2 (en) 2004-03-22 2013-12-23 Mesenchymal stem cells and uses therefor
US14/305,240 US20140328807A1 (en) 2004-03-22 2014-06-16 Mesenchymal Stem Cells and Uses Therefor
US14/334,128 US9694035B2 (en) 2004-03-22 2014-07-17 Mesenchymal stem cells and uses therefor
US14/739,924 US20150272997A1 (en) 2004-03-22 2015-06-15 Mesenchymal Stem Cells and Uses Therefor
US16/204,936 US10729727B2 (en) 2004-03-22 2018-11-29 Mesenchymal stem cells and uses therefor
US16/206,235 US10716814B2 (en) 2004-03-22 2018-11-30 Mesenchymal stem cells and uses therefor
US16/214,485 US11389484B2 (en) 2004-03-22 2018-12-10 Mesenchymal stem cells and uses therefor
US16/811,900 US10960025B2 (en) 2004-03-22 2020-03-06 Mesenchymal stem cells and uses therefor
US16/815,784 US10828334B1 (en) 2004-03-22 2020-03-11 Mesenchymal stem cells and uses therefor
US17/836,786 US20230076630A1 (en) 2004-03-22 2022-06-09 Mesenchymal stem cells and uses therefor

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US55511804P 2004-03-22 2004-03-22
US11/080,298 US20050239897A1 (en) 2004-03-22 2005-03-15 Mesenchymal stem cells and uses therefor
US11/541,853 US20080213227A1 (en) 2004-03-22 2006-10-02 Mesenchymal stem cells and uses therefor

Related Child Applications (4)

Application Number Title Priority Date Filing Date
US11/541,853 Continuation-In-Part US20080213227A1 (en) 2004-03-22 2006-10-02 Mesenchymal stem cells and uses therefor
US11/541,853 Continuation US20080213227A1 (en) 2004-03-22 2006-10-02 Mesenchymal stem cells and uses therefor
US12/323,129 Continuation US20090180997A1 (en) 2004-03-22 2008-11-25 Mesenchymal Stem Cells And Uses Therefor
US12/974,125 Continuation US20110142807A1 (en) 2004-03-22 2010-12-21 Mesenchymal Stem Cells and Uses Therefor

Publications (1)

Publication Number Publication Date
US20050239897A1 true US20050239897A1 (en) 2005-10-27

Family

ID=39772836

Family Applications (21)

Application Number Title Priority Date Filing Date
US11/080,298 Abandoned US20050239897A1 (en) 2004-03-22 2005-03-15 Mesenchymal stem cells and uses therefor
US11/541,853 Abandoned US20080213227A1 (en) 2004-03-22 2006-10-02 Mesenchymal stem cells and uses therefor
US12/091,387 Abandoned US20090208463A1 (en) 2004-03-22 2007-09-26 Mesenchymal stem cells and uses therefor
US12/323,129 Abandoned US20090180997A1 (en) 2004-03-22 2008-11-25 Mesenchymal Stem Cells And Uses Therefor
US12/727,971 Abandoned US20100172885A1 (en) 2004-03-22 2010-03-19 Multipotent Adult Stem Cells And Uses of Multipotent Adult Stem Cells To Treat Inflammation
US12/908,119 Abandoned US20110027238A1 (en) 2004-03-22 2010-10-20 Mesenchymal Stem Cells and Uses Therefor
US12/974,125 Abandoned US20110142807A1 (en) 2004-03-22 2010-12-21 Mesenchymal Stem Cells and Uses Therefor
US13/222,701 Abandoned US20110311496A1 (en) 2004-03-22 2011-08-31 Mesenchymal stem cells and uses therefor
US13/222,831 Abandoned US20110318315A1 (en) 2004-03-22 2011-08-31 Mesenchymal stem cells and uses therefor
US13/222,778 Abandoned US20110318314A1 (en) 2004-03-22 2011-08-31 Mesenchymal stem cells and uses therefor
US14/087,830 Active US9943547B2 (en) 2004-03-22 2013-11-22 Mesenchymal stem cells and uses therefor
US14/138,577 Active US10668101B2 (en) 2004-03-22 2013-12-23 Mesenchymal stem cells and uses therefor
US14/305,240 Abandoned US20140328807A1 (en) 2004-03-22 2014-06-16 Mesenchymal Stem Cells and Uses Therefor
US14/334,128 Active US9694035B2 (en) 2004-03-22 2014-07-17 Mesenchymal stem cells and uses therefor
US14/739,924 Abandoned US20150272997A1 (en) 2004-03-22 2015-06-15 Mesenchymal Stem Cells and Uses Therefor
US16/204,936 Active US10729727B2 (en) 2004-03-22 2018-11-29 Mesenchymal stem cells and uses therefor
US16/206,235 Active US10716814B2 (en) 2004-03-22 2018-11-30 Mesenchymal stem cells and uses therefor
US16/214,485 Active 2026-09-15 US11389484B2 (en) 2004-03-22 2018-12-10 Mesenchymal stem cells and uses therefor
US16/811,900 Active US10960025B2 (en) 2004-03-22 2020-03-06 Mesenchymal stem cells and uses therefor
US16/815,784 Active US10828334B1 (en) 2004-03-22 2020-03-11 Mesenchymal stem cells and uses therefor
US17/836,786 Pending US20230076630A1 (en) 2004-03-22 2022-06-09 Mesenchymal stem cells and uses therefor

Family Applications After (20)

Application Number Title Priority Date Filing Date
US11/541,853 Abandoned US20080213227A1 (en) 2004-03-22 2006-10-02 Mesenchymal stem cells and uses therefor
US12/091,387 Abandoned US20090208463A1 (en) 2004-03-22 2007-09-26 Mesenchymal stem cells and uses therefor
US12/323,129 Abandoned US20090180997A1 (en) 2004-03-22 2008-11-25 Mesenchymal Stem Cells And Uses Therefor
US12/727,971 Abandoned US20100172885A1 (en) 2004-03-22 2010-03-19 Multipotent Adult Stem Cells And Uses of Multipotent Adult Stem Cells To Treat Inflammation
US12/908,119 Abandoned US20110027238A1 (en) 2004-03-22 2010-10-20 Mesenchymal Stem Cells and Uses Therefor
US12/974,125 Abandoned US20110142807A1 (en) 2004-03-22 2010-12-21 Mesenchymal Stem Cells and Uses Therefor
US13/222,701 Abandoned US20110311496A1 (en) 2004-03-22 2011-08-31 Mesenchymal stem cells and uses therefor
US13/222,831 Abandoned US20110318315A1 (en) 2004-03-22 2011-08-31 Mesenchymal stem cells and uses therefor
US13/222,778 Abandoned US20110318314A1 (en) 2004-03-22 2011-08-31 Mesenchymal stem cells and uses therefor
US14/087,830 Active US9943547B2 (en) 2004-03-22 2013-11-22 Mesenchymal stem cells and uses therefor
US14/138,577 Active US10668101B2 (en) 2004-03-22 2013-12-23 Mesenchymal stem cells and uses therefor
US14/305,240 Abandoned US20140328807A1 (en) 2004-03-22 2014-06-16 Mesenchymal Stem Cells and Uses Therefor
US14/334,128 Active US9694035B2 (en) 2004-03-22 2014-07-17 Mesenchymal stem cells and uses therefor
US14/739,924 Abandoned US20150272997A1 (en) 2004-03-22 2015-06-15 Mesenchymal Stem Cells and Uses Therefor
US16/204,936 Active US10729727B2 (en) 2004-03-22 2018-11-29 Mesenchymal stem cells and uses therefor
US16/206,235 Active US10716814B2 (en) 2004-03-22 2018-11-30 Mesenchymal stem cells and uses therefor
US16/214,485 Active 2026-09-15 US11389484B2 (en) 2004-03-22 2018-12-10 Mesenchymal stem cells and uses therefor
US16/811,900 Active US10960025B2 (en) 2004-03-22 2020-03-06 Mesenchymal stem cells and uses therefor
US16/815,784 Active US10828334B1 (en) 2004-03-22 2020-03-11 Mesenchymal stem cells and uses therefor
US17/836,786 Pending US20230076630A1 (en) 2004-03-22 2022-06-09 Mesenchymal stem cells and uses therefor

Country Status (8)

Country Link
US (21) US20050239897A1 (fr)
EP (10) EP1727892B1 (fr)
JP (2) JP2007530543A (fr)
KR (1) KR20090065478A (fr)
CN (1) CN101384702A (fr)
AU (3) AU2005227295A1 (fr)
CA (2) CA2564679C (fr)
WO (2) WO2005093044A1 (fr)

Cited By (59)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020160510A1 (en) * 2001-02-14 2002-10-31 Hariri Robert J. Renovation and repopulation of decellularized tissues and cadaveric organs by stem cells
US20050019908A1 (en) * 2000-12-06 2005-01-27 Anthrogenesis Corporation Post-partum mammalian placenta, its use and placental stem cells therefrom
US20070207130A1 (en) * 2006-03-01 2007-09-06 Calvin Cao Stem cell therapy to treat symptoms of avian flu and other diseases
US20080095749A1 (en) * 2004-03-22 2008-04-24 Sudeepta Aggarwal Mesenchymal stem cells and uses therefor
WO2008042174A3 (fr) * 2004-03-22 2008-06-19 Osiris Therapeutics Inc Cellules souches mésenchymateuses et leurs utilisations
US20080159995A1 (en) * 2006-10-03 2008-07-03 Monica Silverstone Spiteri Treatment of fibrosis
US20080260703A1 (en) * 2007-04-23 2008-10-23 Medistem Labortories Treatment of Insulin Resistance and Diabetes
US20080292600A1 (en) * 2005-06-17 2008-11-27 Song Sun Uk Treatment of graft-versus-host disease
US20080311088A1 (en) * 2006-02-01 2008-12-18 Samsungn Life Public Welfare Foundation Method of Treating Lung Diseases Using Cells Separated Or Proliferated From Umbilical Cord Blood
WO2009114860A2 (fr) * 2008-03-14 2009-09-17 The Board Of Trustees Of The University Of Illinois Cellules souches mésenchymateuses activées pour la prévention et la réparation d’états inflammatoires
US20100008992A1 (en) * 2006-05-19 2010-01-14 Medistem Laboratories, Inc. Treatment of disc degenerative disease and compositions for same
US7682803B2 (en) 2005-10-13 2010-03-23 Anthrogenesis Corporation Immunomodulation using placental stem cells
US7700090B2 (en) 2002-02-13 2010-04-20 Anthrogenesis Corporation Co-culture of placental stem cells and stem cells from a second source
US20100189750A1 (en) * 2007-09-12 2010-07-29 Yeda Research And Development Co. Ltd. Methods of treating tumors in immune-privileged sites
US20110020293A1 (en) * 2009-07-21 2011-01-27 Abt Holding Company Use of Stem Cells to Reduce Leukocyte Extravasation
US20110020291A1 (en) * 2007-11-17 2011-01-27 Debrabrata Banerjee Use of stem cells for wound healing
US20110104100A1 (en) * 2007-10-04 2011-05-05 Medistem Laboratories, Inc. Compositions and methods of stem cell therapy for autism
US7976836B2 (en) 2000-12-06 2011-07-12 Anthrogenesis Corporation Treatment of stroke using placental stem cells
US7993918B2 (en) 2006-08-04 2011-08-09 Anthrogenesis Corporation Tumor suppression using placental stem cells
US20110262393A1 (en) * 2008-11-14 2011-10-27 Medipost Co., Ltd. Composition comprising mesenchymal stem cells or culture solution of mesenchymal stem cells for the prevention or treatment of neural diseases
US20110262402A1 (en) * 2007-09-07 2011-10-27 Masahiko Kuroda Therapeutic and prophylactic agents for arthritis
US8057789B2 (en) 2002-02-13 2011-11-15 Anthrogenesis Corporation Placental stem cells derived from post-partum mammalian placenta, and uses and methods of treatment using said cells
US8057788B2 (en) 2000-12-06 2011-11-15 Anthrogenesis Corporation Placental stem cell populations
US20110283371A1 (en) * 2008-12-09 2011-11-17 University Of Southern California Stem Cell Modified Animal Model for Aging-Related Degenerations, Stem Cell Based Methods and Compositions for Extending Lifespan and Treating SLE-Like Autoimmune Diseases
US20120020931A1 (en) * 2010-06-02 2012-01-26 Rutgers, The State University Of New Jersey Therapeutic encapsulated embryonic stem cells and mesenchymal stromal cells
US20120027730A1 (en) * 2008-08-04 2012-02-02 Consejo Superior De Investigaciones Cientificas Uses of mesenchymal stem cells
US20120148544A1 (en) * 2007-06-15 2012-06-14 Garnet Biotherapeutics, Inc. Treatment of Diseases and Disorders Using Self-Renewing Colony Forming Cells Cultured and Expanded In Vitro
US20120288480A1 (en) * 2011-02-22 2012-11-15 Taipei Medical University Cell population comprising orbital fat-derived stem cells (ofscs) and their isolation and applications
US8367409B2 (en) 2008-11-19 2013-02-05 Anthrogenesis Corporation Amnion derived adherent cells
US8460650B2 (en) 2007-02-12 2013-06-11 Anthrogenesis Corporation Treatment of inflammatory diseases using placental stem cells
US20130230454A1 (en) * 2007-03-27 2013-09-05 Cardiovascular Biotherapeutics, Inc. Therapeutic Angiogenesis for Treatment of the Spine and Other Tissues
US8562973B2 (en) 2010-04-08 2013-10-22 Anthrogenesis Corporation Treatment of sarcoidosis using placental stem cells
US8728805B2 (en) 2008-08-22 2014-05-20 Anthrogenesis Corporation Methods and compositions for treatment of bone defects with placental cell populations
US20140248244A1 (en) * 2006-01-13 2014-09-04 Mesoblast International Sarl Mesenchymal Stem Cells Expressing TNF-alpha Receptors
US8828376B2 (en) 2008-08-20 2014-09-09 Anthrogenesis Corporation Treatment of stroke using isolated placental cells
US8969315B2 (en) 2010-12-31 2015-03-03 Anthrogenesis Corporation Enhancement of placental stem cell potency using modulatory RNA molecules
US9011840B2 (en) 2008-03-14 2015-04-21 The Board Of Trustees Of The University Of Illinois Activated mesenchymal stem cells for wound healing and impaired tissue regeneration
US9040035B2 (en) 2011-06-01 2015-05-26 Anthrogenesis Corporation Treatment of pain using placental stem cells
US20150224146A1 (en) * 2005-09-23 2015-08-13 Tigenix, S.A.U. Cell populations having immunoregulatory activity, method for isolation and uses
US9121007B2 (en) 2010-01-26 2015-09-01 Anthrogenesis Corporatin Treatment of bone-related cancers using placental stem cells
US9254302B2 (en) 2010-04-07 2016-02-09 Anthrogenesis Corporation Angiogenesis using placental stem cells
US20160120908A1 (en) * 2013-05-08 2016-05-05 Shanghai Institutes For Biological Sciences, Chinese Academy Of Sciences Application of mesenchymal stem cells in prophylaxis or treatment of stress response-induced weakened immunity
US20160263162A1 (en) * 2007-04-06 2016-09-15 Xon Cells, Inc. Stem cell therapy for the treatment of autism and other disorders
US9517248B2 (en) 2007-09-19 2016-12-13 Pluristem Ltd. Adherent cells from adipose or placenta tissues and use thereof in therapy
US9518251B2 (en) 2014-09-17 2016-12-13 Gwo Xi Stem Cell Applied Technology Co., Ltd. Method for enhancing therapeutic effect of stem cells on autoimmune diseases, cardiovascular diseases, and/or hematological diseases
US9861660B2 (en) 2013-04-12 2018-01-09 Saverio LaFrancesca Organs for transplantation
US9925221B2 (en) 2011-09-09 2018-03-27 Celularity, Inc. Treatment of amyotrophic lateral sclerosis using placental stem cells
US9937208B2 (en) 2010-05-12 2018-04-10 Abt Holding Company Modulation of splenocytes in cell therapy
US20180214489A1 (en) * 2017-01-27 2018-08-02 Neil Riordan Mesenchymal stem cells with enhanced efficacy in treatment of autoimmunity particularly rheumatoid arthritis
US10104880B2 (en) 2008-08-20 2018-10-23 Celularity, Inc. Cell composition and methods of making the same
US10272118B2 (en) 2013-02-12 2019-04-30 Replicel Life Sciences Inc. Compositions and methods for treating and repairing tendons
US10351826B2 (en) 2001-09-21 2019-07-16 Garnet Biotherapeutics, Inc. Cell populations which co-express CD49c and CD90
US10357518B2 (en) 2016-03-14 2019-07-23 Tigenix S.A.U. Adipose tissue-derived stromal stem cells for use in treating refractory complex perianal fistulas in Crohn's disease
US10500233B2 (en) 2014-02-12 2019-12-10 Replicel Life Sciences Inc. Compositions and methods for treating bone, joints and cartilage
US10548924B2 (en) 2004-08-25 2020-02-04 Tigenix, S.A.U. Use of adipose tissue-derived stromal stem cells in treating fistula
US10624952B2 (en) 2007-03-27 2020-04-21 Cardiovascular Biotherapeutics, Inc. Systems and methods for angiogenic treatment in wound healing
US10980858B2 (en) 2016-06-20 2021-04-20 Fujifilm Corporation Trophic factor releasing agent and inflammatory disease treating agent
CN113396333A (zh) * 2019-01-31 2021-09-14 普里梅真生物技术有限责任公司 使用间充质干细胞和免疫调节治疗特应性皮炎
US20210386833A1 (en) * 2018-10-04 2021-12-16 National Institute For Materials Science Angiogenesis promoter and therapeutic method

Families Citing this family (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7514074B2 (en) * 1997-07-14 2009-04-07 Osiris Therapeutics, Inc. Cardiac muscle regeneration using mesenchymal stem cells
AUPR298901A0 (en) 2001-02-07 2001-03-08 McComb Foundation, Inc., The Cell suspension preparation technique and device
ES2643076T3 (es) * 2004-03-22 2017-11-21 Mesoblast International Sàrl Células madre mesenquimales y sus usos
ES2313805B1 (es) 2004-10-04 2009-12-23 Cellerix, S.L. Identificacion y aislamiento de celulas multipotentes de tejido mesenquimal no osteocondral.
EP2023943A2 (fr) * 2006-04-28 2009-02-18 Tulane University Health Sciences Center Méthodes pour traiter le diabète
EP2129775A1 (fr) 2007-02-12 2009-12-09 Anthrogenesis Corporation Hepatocytes et chondrocytes provenant de cellules souches placentaires adherentes ; et populations de cellules enrichies avec des cellules souches placentaires cd34+, cd45-
ES2507507T3 (es) * 2007-05-24 2014-10-15 Apceth Gmbh & Co. Kg Células madre mesenquimales CD34 negativas modificadas genéticamente para el tratamiento de tumores
US9200253B1 (en) 2007-08-06 2015-12-01 Anthrogenesis Corporation Method of producing erythrocytes
WO2009023566A2 (fr) 2007-08-09 2009-02-19 Genzyme Corporation Procédé de traitement d'une maladie auto-immune avec des cellules souches mésenchymateuses
KR20230065354A (ko) 2007-09-28 2023-05-11 셀룰래리티 인코포레이티드 인간 태반 관류액 및 인간 태반-유래 중간체 천연 킬러 세포를 사용한 종양 억제 방법
US20100247577A1 (en) 2007-10-17 2010-09-30 Txcell Tr1 cells, mesenchymal stem cells and uses thereof
CA2710081C (fr) * 2007-12-21 2015-11-24 Bone Therapeutics S.A. Cellules de formation d'os humain dans le traitement de maladies rhumatismales inflammatoires
JP5541845B2 (ja) * 2008-03-28 2014-07-09 Ｊｃｒファーマ株式会社 アトピー性皮膚炎治療剤
US20110150845A1 (en) * 2008-05-02 2011-06-23 Massachusetts Institute Of Technology Methods and compositions for modulating immunological tolerance
RU2515156C2 (ru) 2008-05-27 2014-05-10 Плуристем Лтд. Способы лечения воспалительных заболеваний ободочной кишки
AU2015268704B2 (en) * 2008-08-04 2017-08-10 Consejo Superior De Investigaciones Cientificas Uses of mesenchymal stem cells
ES2608974T3 (es) * 2008-08-14 2017-04-17 Mesoblast International Sàrl Composiciones de células madre mesenquimales purificadas
US8343480B2 (en) * 2008-11-14 2013-01-01 Howmedica Osteonics Corp. Administration of stem or progenitor cells to a joint to enhance recovery from joint surgery
US9192695B2 (en) 2008-11-20 2015-11-24 Allosource Allografts combined with tissue derived stem cells for bone healing
US8309343B2 (en) 2008-12-01 2012-11-13 Baxter International Inc. Apparatus and method for processing biological material
AU2010266263B2 (en) 2009-07-02 2016-05-19 Celularity Inc. Method of producing erythrocytes without feeder cells
US8932852B2 (en) 2009-08-14 2015-01-13 Case Western Reserve University Compositions and methods of treating inflammatory bowel disease
WO2011047345A2 (fr) * 2009-10-15 2011-04-21 Tai June Yoo Méthodes de traitement de maladies ou d'affections faisant appel à des cellules souches mésenchymateuses
KR101301262B1 (ko) * 2009-10-23 2013-08-27 가톨릭대학교 산학협력단 ＴＧＦβ를 코딩하는 뉴클레오티드 서열이 도입된 간엽줄기세포 및 그의 용도
CN102048756B (zh) * 2009-11-04 2014-02-19 中国医学科学院基础医学研究所 人脂肪来源的间充质干细胞在肾脏、眼底疾病中的用途
CA2781194A1 (fr) * 2009-11-19 2011-05-26 Regents Of The University Of Minnesota Diminution de l'inflammation grace au recours a une therapie cellulaire
DK2510084T3 (da) * 2009-12-08 2020-04-27 The Board Of Trustees Of The Univ Of Illionis Stamcelleimmunmoduleringsanvendelsesfremgangsmåder og apparat
US20140286911A1 (en) 2013-03-15 2014-09-25 Allosource Cell repopulated collagen matrix for soft tissue repair and regeneration
EP2539436B1 (fr) * 2010-02-25 2021-09-22 ABT Holding Company Modulation d'activation de macrophages
EP2575831B1 (fr) * 2010-05-27 2016-04-20 Pluristem Ltd. Régénération de muscle squelettique au moyen de cellules souches mésenchymateuses
KR20230096132A (ko) 2010-07-13 2023-06-29 셀룰래리티 인코포레이티드 천연 킬러 세포의 생성 방법
WO2012009581A2 (fr) * 2010-07-14 2012-01-19 University Of Southern California Compositions pharmaceutiques comprenant des cellules souches mésenchymateuses d'origine gingivale et méthodes de traitement d'inflammation, cicatrisation de plaies et hypersensibilité de contact
BR112013004917A2 (pt) * 2010-08-31 2016-09-20 Cook General Biotechnology Llc terapias de células tronco alogênicas sistêmicas para tratamento de doenças em animais.
EP3679939A1 (fr) * 2010-10-08 2020-07-15 Mesoblast International Sàrl Préparations de msc améliorées
ES2479544T1 (es) * 2011-01-12 2014-08-20 Tigenix, S.A.U. Células madre mesenquimales derivadas de tejido adiposo para administración intralinfática en enfermedades autoimmunes e inflamatorias
CA2824553A1 (fr) 2011-01-19 2012-07-26 The Regents Of The University Of California Cellules somatiques a potentiel inne de pluripotence
KR20120095022A (ko) * 2011-02-18 2012-08-28 가톨릭대학교 산학협력단 간엽줄기세포 및 면역조절 ｔ 세포를 유효성분으로 포함하는 이식편대숙주질환 예방 또는 치료용 세포치료제 조성물
US8709401B2 (en) 2011-02-25 2014-04-29 Howmedica Osteonics Corp. Primed stem cells and uses thereof to treat inflammatory conditions in joints
DK2788014T3 (da) 2011-12-09 2020-01-02 Metabolic Pharmaceuticals Pty Ltd Anvendelse af væksthormonfragmenter
CN102552880A (zh) * 2011-12-14 2012-07-11 南方医科大学 一种促进皮肤创面愈合的生物制剂
CN103191154B (zh) * 2012-01-06 2015-09-09 上海交通大学医学院 充质干细胞及其提取方法在制备银屑病的药物中的应用
GB201202319D0 (en) * 2012-02-10 2012-03-28 Orbsen Therapeutics Ltd Stromal stem cells
CN104685049A (zh) * 2012-03-22 2015-06-03 埃维塔医疗有限公司 细胞悬液及其用途
WO2013146992A1 (fr) 2012-03-29 2013-10-03 日本ケミカルリサーチ株式会社 Procédé de fabrication de cellules souches pluripotentes dérivées de la pulpe dentaire
WO2014018230A2 (fr) * 2012-07-25 2014-01-30 Albert Einstein College Of Medicine Of Yeshiva University Procédés pour isoler des cellules souches mésenchymateuses humaines
CN103585177A (zh) * 2012-08-13 2014-02-19 首都医科大学附属北京口腔医院 间充质干细胞和基因修饰的间充质干细胞的用途
JP6286445B2 (ja) 2012-12-24 2018-02-28 セル・アイディアズ・ピーティーワイ・リミテッド がんの治療のためのワクチン及びワクチン有効性を増強するための組成物
WO2014113704A2 (fr) * 2013-01-18 2014-07-24 Escape Therapeutics, Inc. Amélioration de la différenciation de cellules souches mésenchymateuses
EP3622960A1 (fr) 2013-02-05 2020-03-18 Celularity, Inc. Cellules tueuses naturelles placentaires
US20140271568A1 (en) * 2013-03-12 2014-09-18 Hawking Biological Technology Co., Ltd Method and kit for providing an increased expression of telomerase, brain-derived neurotrophic factor, stromal cell-derived factor-1, cxc chemokine receptor 4, and/or immune regulatory factor of stem cell
WO2014143383A1 (fr) 2013-03-13 2014-09-18 Agilent Technologies, Inc. Transposome attaché à un véhicule d'administration de gène
AU2013205148B2 (en) 2013-03-14 2014-10-30 AVITA Medical Americas, LLC Systems and methods for tissue processing and preparation of cell suspension therefrom
ES2748825T3 (es) * 2013-03-15 2020-03-18 Tigenix S A U Biomarcadores de linfocitos para determinar la respuesta clínica a la terapia celular
JP6765961B2 (ja) * 2013-11-04 2020-10-07 ベクトン・ディキンソン・アンド・カンパニーＢｅｃｔｏｎ， Ｄｉｃｋｉｎｓｏｎ Ａｎｄ Ｃｏｍｐａｎｙ 多能性間質細胞集団の免疫調節ポテンシャル
US20160129531A1 (en) * 2014-01-13 2016-05-12 Camarc Llc Electrode of a welding torch
MX2017000142A (es) * 2014-06-30 2017-07-28 Tigenix S A U Celulas estromales mesenquimatosas para tratar el sindrome de respuesta inflamatoria sistemica.
JP6452107B2 (ja) 2014-09-05 2019-01-16 国立大学法人 東京大学 糖尿病性皮膚潰瘍治療のための多能性幹細胞
US20160095885A1 (en) 2014-10-01 2016-04-07 WibiWorks Therapeutics, Inc. Induction Medium & Methods for Stem Cell Culture & Therapy
CN104357383A (zh) * 2014-10-11 2015-02-18 张炳强 人脂肪间充质干细胞制备方法及其在制备疾病药物的应用
RU2644650C2 (ru) 2014-12-01 2018-02-13 Общество с ограниченной ответственностью "Т-Хелпер Клеточные Технологии" Материал стволовых клеток и способ его получения
EP3271396B1 (fr) 2015-03-20 2022-03-16 Orbsen Therapeutics Limited Modulateurs de syndecan-2 et utilisations de ceux-ci
WO2016153847A1 (fr) * 2015-03-20 2016-09-29 Rediens, Inc. Systèmes et procédés d'administration à du tissu osseux
EP3286562B1 (fr) * 2015-04-24 2020-08-12 TiGenix, S.A.U. Biomarqueurs pour déterminer la réponse clinique à une thérapie cellulaire
CN108430480B (zh) 2015-09-15 2022-08-02 康干细胞生物科技有限公司 一种包含过表达sod3的干细胞作为活性成分的炎症性疾病的预防或治疗用组合物
EP3922253A1 (fr) 2016-01-15 2021-12-15 Orbsen Therapeutics Limited Compositions d'exosomes à base de sdc-2 et leurs procédés d'isolement et d'utilisation
US10967006B2 (en) 2016-01-21 2021-04-06 Abt Holding Company Stem cells for wound healing
CN108884441B (zh) 2016-03-16 2022-05-06 洋蓟治疗有限公司 集落形成培养基及其用途
RU2708329C2 (ru) 2016-05-31 2019-12-05 Общество с ограниченной ответственностью "Т-Хелпер Клеточные Технологии" Материал стволовых клеток, композиции и способы применения
KR101816246B1 (ko) * 2016-09-07 2018-01-08 에스씨엠생명과학 주식회사 염증 자극된 중간엽 줄기세포를 포함하는 면역질환 또는 염증 질환의 예방 또는 치료용 약학적 조성물
WO2018092769A1 (fr) 2016-11-15 2018-05-24 株式会社カネカ Population de cellules contenant des cellules souches mésenchymateuses dérivées d'appendices fœtaux, son procédé de production, et composition médicinale
EP3652305A2 (fr) 2017-07-14 2020-05-20 Orbsen Therapeutics Limited Procédés d'isolement et d'utilisation de cellules souches stromales cd39
MX2020006321A (es) 2017-12-22 2020-09-18 Chiesi Farm Spa Celulas estromales mesenquimales y metodos para obtener celulas estromales mesenquimales del cordon umbilical.
US20200368291A1 (en) 2017-12-28 2020-11-26 Kaneka Corporation Cell population including adhesive stem cells, production method therefor and pharmaceutical composition
JP7217533B2 (ja) * 2018-01-24 2023-02-03 学校法人順天堂大学 間葉系幹細胞による処置の効果を増幅するための組成物
US20210154230A1 (en) * 2018-05-04 2021-05-27 Spinalcyte, Llc Intradiscal t-regulatory cell administration for treatment of disc degenerative disease
CN108646035B (zh) * 2018-05-18 2021-06-11 北京亦科诺生物科技有限公司 ***1的新应用
KR20210008101A (ko) * 2018-06-05 2021-01-20 메디포스트(주) 히알루론산과 줄기세포를 포함하는 연골손상 관련 질환 치료용 약학 조성물
WO2019240962A1 (fr) * 2018-06-14 2019-12-19 Abraham J And Phyllis Katz Cord Blood Foundation Isolement de cellules stromales mésenchymateuses à partir de sang de cordon ombilical
WO2020182935A1 (fr) * 2019-03-12 2020-09-17 Global Stem Cell Technology Cellules souches mésenchymateuses immunomodulatrices
WO2020190023A2 (fr) * 2019-03-19 2020-09-24 에스씨엠생명과학 주식회사 Procédé de traitement de dermatite atopique à l'aide de cellules souches monoclonales
RU2704322C1 (ru) * 2019-06-11 2019-10-28 Федеральное государственное автономное образовательное учреждение высшего образования "Белгородский государственный национальный исследовательский университет" (НИУ "БелГУ") Крем с секретомом мультипотентных мезенхимальных стромальных клеток для коррекции псориазиформного воспаления в эксперименте
JPWO2020251020A1 (fr) 2019-06-14 2020-12-17
JP2023517035A (ja) * 2020-03-05 2023-04-21 メゾブラスト・インターナショナル・エスアーエールエル 間葉系統前駆または幹細胞を使用して炎症性肺疾患を治療するための方法
JPWO2021210515A1 (fr) * 2020-04-13 2021-10-21
CN111557952A (zh) * 2020-05-28 2020-08-21 澳门大学 间充质干细胞在制备用于促进脂肪移植的制剂中的应用
CN111979186B (zh) * 2020-08-21 2022-04-08 遵义医科大学附属医院 一种快速高效体外扩增人间充质干细胞的方法及应用
CN112076217A (zh) * 2020-10-26 2020-12-15 重庆医科大学附属第一医院 一种间充质干细胞来源的抗炎症氧化脂质组合物的制备方法
CN115433709A (zh) * 2022-06-13 2022-12-06 南京艾尔普再生医学科技有限公司 一种用于预测心肌细胞移植免疫排斥反应的体外实验模型

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5486359A (en) * 1990-11-16 1996-01-23 Osiris Therapeutics, Inc. Human mesenchymal stem cells
US6010696A (en) * 1990-11-16 2000-01-04 Osiris Therapeutics, Inc. Enhancing hematopoietic progenitor cell engraftment using mesenchymal stem cells
US6077987A (en) * 1997-09-04 2000-06-20 North Shore-Long Island Jewish Research Institute Genetic engineering of cells to enhance healing and tissue regeneration
US6355239B1 (en) * 1998-03-13 2002-03-12 Osiris Therapeutics, Inc. Uses for non-autologous mesenchymal stem cells
US20020110544A1 (en) * 1998-05-13 2002-08-15 Victor M. Goldberg Osteoarthritis cartilage regeneration
US20030118567A1 (en) * 1999-03-26 2003-06-26 Stewart Duncan John Cell-based therapy for the pulmonary system
US20050093044A1 (en) * 2003-10-29 2005-05-05 Kangguo Cheng DRAM cell with buried collar and self-aligned buried strap
US20060112365A1 (en) * 2004-11-19 2006-05-25 Fujitsu Limited Design support apparatus, design support program and design support method for supporting design of semiconductor integrated circuit
US20070084354A1 (en) * 2005-10-14 2007-04-19 Hsiao Ming Folding grill

Family Cites Families (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0651641B2 (ja) * 1983-08-29 1994-07-06 株式会社ミドリ十字 ガンマ・インターフェロン組成物
JPS6048933U (ja) 1983-09-12 1985-04-06 株式会社大隈鐵工所 研削盤ベツド上面のしぶき止めカバ−
EP0302862A1 (fr) 1986-03-17 1989-02-15 Schering Corporation Traitement de cancers a l'aide de l'interferon gamma
US5843425A (en) * 1992-02-19 1998-12-01 The General Hospital Corporation Transplantation and graft-versus-host-disease
JPH06508528A (ja) * 1992-03-23 1994-09-29 ネクセル　セラピューティクス　インコーポレーテッド インビトロ由来ヒト好中球前駆体細胞
US5382514A (en) 1992-03-31 1995-01-17 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services In vivo angiogenesis assay
DE69637185T2 (de) 1995-03-28 2008-04-10 Thomas Jefferson University Isolierte Stromazellen und Methoden zu deren Verwendung
US6653134B2 (en) 1995-03-28 2003-11-25 Cp Hahnemann University Isolated stromal cells for use in the treatment of diseases of the central nervous system
US6974571B2 (en) * 1995-03-28 2005-12-13 Thomas Jefferson University Isolated stromal cells and methods of using the same
WO1997041208A1 (fr) 1996-04-26 1997-11-06 Case Western Reserve University Regeneration de la peau au moyen des cellules souches mesenchymateuses
US6165785A (en) 1996-05-24 2000-12-26 University Of Cincinnati Bone marrow cultures for developing suppressor and stimulator cells for research and therapeutic applications
EP0941027A4 (fr) * 1996-11-15 2000-08-09 Osiris Therapeutics Inc Compositions mixtes de cellules MSC et de précurseurs de mégacaryocytes et procédé pour isoler les cellules MSC associées aux mégacaryocytes, en séparant les Mégacaryocytes
US20030103951A1 (en) 1997-07-14 2003-06-05 Osiris Therapeutics, Inc. Cardiac muscle regeneration using mesenchymal stem cells
US6328960B1 (en) * 1998-03-18 2001-12-11 Osiris Therapeutics, Inc. Mesenchymal stem cells for prevention and treatment of immune responses in transplantation
US6368636B1 (en) * 1998-03-18 2002-04-09 Osiris Therapeutics, Inc. Mesenchymal stem cells for prevention and treatment of immune responses in transplantation
WO1999051247A1 (fr) * 1998-04-03 1999-10-14 Osiris Therapeutics, Inc. Utilisation de cellules souches mesenchimateuses pour induire une apoptose des lymphocytes t
CA2326838C (fr) * 1998-04-03 2008-12-23 Osiris Therapeutics, Inc. Cellules souches mesenchimateuses utilisees comme immunodepresseurs
JP2002521493A (ja) * 1998-07-31 2002-07-16 ジェンザイム コーポレーション 間葉幹細胞移植による心機能の改善
AU2998300A (en) * 1999-02-17 2000-09-04 United States Surgical Corporation Genetically altered mesenchymal stem cells and methods of use thereof
US20050153442A1 (en) * 1999-03-10 2005-07-14 Adam Katz Adipose-derived stem cells and lattices
EP1165830B1 (fr) * 1999-03-10 2017-07-12 University of Pittsburgh of the Commonwealth System of Higher Education Cellules souches et reseaux derives de tissus adipeux
US8017112B2 (en) 1999-05-14 2011-09-13 Henry Ford Health System Transplantation of bone marrow stromal cells for treatment of neurodegenerative diseases
US6685936B2 (en) 1999-10-12 2004-02-03 Osiris Therapeutics, Inc. Suppressor cells induced by culture with mesenchymal stem cells for treatment of immune responses in transplantation
EP1564292A1 (fr) 2000-01-19 2005-08-17 Parkash S. Gill Compositions renfermant des oligonucléotides antisens dirigés contre le VEGF et méthodes associées
US6528511B2 (en) † 2000-02-18 2003-03-04 Cv Therapeutics, Inc. Partial fatty acid oxidation inhibitors in the treatment of congestive heart failure
ES2300320T3 (es) 2000-02-26 2008-06-16 Artecel, Inc. Celulas madre pluripotentes generadas a partir de celulas del estroma derivadas de tejido adiposo y sus usos.
ES2353061T5 (es) * 2000-04-25 2014-04-07 Osiris Therapeutics, Inc. Reparación de articulaciones utilizando células madre mesenquimatosas
US6936281B2 (en) * 2001-03-21 2005-08-30 University Of South Florida Human mesenchymal progenitor cell
US20040022787A1 (en) 2000-07-03 2004-02-05 Robert Cohen Methods for treating an autoimmune disease using a soluble CTLA4 molecule and a DMARD or NSAID
CA2429502A1 (fr) * 2000-07-26 2002-01-31 Scimed Life Systems, Inc. Angiogenese therapeutique par transplantation de cellules de moelle osseuse dans un tissu ischemique du myocarde ou dans un tissu ischemique du muscle squelettique
US20020045260A1 (en) * 2000-10-17 2002-04-18 Shih-Chieh Hung Method of isolating mesenchymal stem cells
CA2438047A1 (fr) * 2001-02-14 2002-08-22 Hildegard M. Kramer Molleton biocompatible pour hemostase et tissu obtenu par genie tissulaire
DE60231035D1 (de) 2001-04-24 2009-03-19 Ajinomoto Kk Stammzellen und verfahren zu deren trennung
US6549704B2 (en) 2001-06-26 2003-04-15 Corning Incorporated Fabrication of microlensed fiber using doped silicon dioxide
US6905678B2 (en) * 2001-07-07 2005-06-14 Crucell Holland B.V. Gene delivery vectors with cell type specificity for mesenchymal stem cells
EP1279738A1 (fr) * 2001-07-06 2003-01-29 Crucell Holland B.V. Vecteurs de transfert de genes munis d'un tropisme pour des cellules souches mesenchymateuses
EP1430115A1 (fr) * 2001-07-27 2004-06-23 Arhus Amt Cellules souches immortalis es
EP1433487A1 (fr) * 2001-08-22 2004-06-30 National Institute of Advanced Industrial Science and Technology Procede de regeneration osseuse
US20030104997A1 (en) 2001-09-05 2003-06-05 Black Ira B. Multi-lineage directed induction of bone marrow stromal cell differentiation
AU2002359390A1 (en) 2001-11-09 2003-05-19 Artecel Sciences, Inc. Endocrine pancreas differentiation of adipose tissue-derived stromal cells and uses thereof
US6939863B2 (en) 2002-01-04 2005-09-06 Wei-Jan Chen Prevention of atherosclerosis and restenosis
US7687505B2 (en) 2002-01-14 2010-03-30 Board Of Trustees Of The University Of Illinois Use of modified pyrimidine compounds to promote stem cell migration and proliferation
WO2003059272A2 (fr) 2002-01-14 2003-07-24 Henry Ford Health System Matieres issues des cellules stromales de la moelle osseuse destinees a la formation de vaisseaux sanguins et a la production de facteurs angiogeniques et trophiques
US20030161815A1 (en) * 2002-02-12 2003-08-28 Intercytex Limited Cell delivery system
AUPS112802A0 (en) 2002-03-15 2002-04-18 Monash University Methods of inducing differentiation of stem cells into a specific cell lineage
WO2003077865A2 (fr) * 2002-03-15 2003-09-25 Baxter International Inc. Procedes et compositions permettant de diriger des cellules sur des organes cibles
JP2005520511A (ja) * 2002-03-18 2005-07-14 ガミダ セル リミテッド エクスビボ拡大培養された幹細胞における分化を誘導する方法
JP4554940B2 (ja) * 2002-04-03 2010-09-29 直秀 山下 ヒト胎盤由来の間葉系細胞を含む医薬及び該細胞を用いたｖｅｇｆの製造方法
ITTO20020311A1 (it) 2002-04-10 2003-10-10 Medestea Int Spa Procedimento per la preparazione di cellule staminali da tessuto muscolare e tessuto adiposo umano e cellule staminali ottenibili mediante t
US7498171B2 (en) * 2002-04-12 2009-03-03 Anthrogenesis Corporation Modulation of stem and progenitor cell differentiation, assays, and uses thereof
CN1187058C (zh) * 2002-04-16 2005-02-02 中国医学科学院血液学研究所泰达生命科学技术研究中心 用于修复中枢神经损伤的干细胞制剂及其制造方法
US7628988B2 (en) 2002-06-27 2009-12-08 The General Hospital Corporation Methods and compositions for treating type 1 diabetes
US20040009155A1 (en) * 2002-07-12 2004-01-15 Maria Palasis Method for sustaining direct cell delivery
US20050249731A1 (en) 2002-07-16 2005-11-10 Hadi Aslan Methods of implating mesenchymal stem cells for tissue repair and formation
EP1545219A4 (fr) 2002-07-23 2009-09-30 Boston Scient Ltd Therapie cellulaire de regeneration
CA2494040A1 (fr) * 2002-07-29 2004-02-05 Es Cell International Pte Ltd. Procede en plusieurs etapes de differenciation des cellules sensibles a l'insuline positive, au glucose
JP3897343B2 (ja) * 2002-08-01 2007-03-22 株式会社林原生物化学研究所 免疫担当細胞においてインターフェロン−γの産生を誘導する蛋白質
WO2004016779A1 (fr) * 2002-08-17 2004-02-26 Hae-Young Suh Methode de transdifferenciation de cellules souches mesenchymateuses en cellules neuronales
KR20040022134A (ko) * 2002-09-06 2004-03-11 송준석 인간 간엽줄기 세포와 p53 분비 아데노바이러스를 이용한항암치료방법
WO2004022579A2 (fr) * 2002-09-06 2004-03-18 University Of South Florida Apport cellulaire de peptides natriuretiques
WO2004052177A2 (fr) 2002-12-05 2004-06-24 Case Western Reserve University Therapies a base de cellules pour ischemie.
WO2004084950A2 (fr) * 2003-03-24 2004-10-07 Case Western Reserve University Procedes et compositions de ciblage cellulaire
CN1536075A (zh) * 2003-04-09 2004-10-13 中国人民解放军军事医学科学院野战输 一种诱导骨髓间充质干细胞向胰岛样细胞分化的方法
ES2564044T3 (es) * 2003-06-27 2016-03-17 DePuy Synthes Products, Inc. Células posparto derivadas de tejido del cordón umbilical y métodos de preparación y uso de las mismas
WO2005013885A2 (fr) * 2003-08-07 2005-02-17 Healor Ltd. Compositions pharmaceutiques et methodes permettant d'accelerer la cicatrisation de plaies
JP4416737B2 (ja) * 2003-11-20 2010-02-17 株式会社アドバンテスト クロックリカバリ回路及び通信デバイス
US20080095749A1 (en) 2004-03-22 2008-04-24 Sudeepta Aggarwal Mesenchymal stem cells and uses therefor
JP2007530543A (ja) 2004-03-22 2007-11-01 オシリス セラピューティクス，インコーポレイテッド 間葉幹細胞及びその使用法
US7405186B2 (en) 2005-03-25 2008-07-29 Chemsil Silicones, Inc. Lubricant compositions, condom products and methods of making same
WO2006112365A1 (fr) 2005-04-14 2006-10-26 Japan Health Sciences Foundation Traitement de l'emphyseme pulmonaire par cellule souche mesenchymateuse
US20070253931A1 (en) 2006-01-12 2007-11-01 Osiris Therapeutics, Inc. Use of mesenchymal stem cells for treating genetic diseases and disorders
ES2415855T3 (es) 2006-01-13 2013-07-29 Osiris Therapeutics, Inc. Células troncales mesenquimatosas que expresan el receptor de TNF
US20090274665A1 (en) 2006-04-27 2009-11-05 Cell Therapy Technologies, Inc. Stem Cells For Treating Lung Diseases
JP5371764B2 (ja) 2006-10-06 2013-12-18 コーニンクレッカ フィリップス エヌ ヴェ 照明素子のための電源装置及び照明素子に電力を供給するための方法
US8029805B2 (en) 2008-07-25 2011-10-04 Her Majesty The Queen In Right Of Canada, As Represented By The Minister Of National Defence Recombinant B. pseudomallei adhesin protein and methods and uses thereof
ES2608974T3 (es) 2008-08-14 2017-04-17 Mesoblast International Sàrl Composiciones de células madre mesenquimales purificadas
EP3679939A1 (fr) 2010-10-08 2020-07-15 Mesoblast International Sàrl Préparations de msc améliorées

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5486359A (en) * 1990-11-16 1996-01-23 Osiris Therapeutics, Inc. Human mesenchymal stem cells
US6010696A (en) * 1990-11-16 2000-01-04 Osiris Therapeutics, Inc. Enhancing hematopoietic progenitor cell engraftment using mesenchymal stem cells
US6077987A (en) * 1997-09-04 2000-06-20 North Shore-Long Island Jewish Research Institute Genetic engineering of cells to enhance healing and tissue regeneration
US6355239B1 (en) * 1998-03-13 2002-03-12 Osiris Therapeutics, Inc. Uses for non-autologous mesenchymal stem cells
US20020110544A1 (en) * 1998-05-13 2002-08-15 Victor M. Goldberg Osteoarthritis cartilage regeneration
US20030118567A1 (en) * 1999-03-26 2003-06-26 Stewart Duncan John Cell-based therapy for the pulmonary system
US20050093044A1 (en) * 2003-10-29 2005-05-05 Kangguo Cheng DRAM cell with buried collar and self-aligned buried strap
US20060112365A1 (en) * 2004-11-19 2006-05-25 Fujitsu Limited Design support apparatus, design support program and design support method for supporting design of semiconductor integrated circuit
US20070084354A1 (en) * 2005-10-14 2007-04-19 Hsiao Ming Folding grill

Cited By (123)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8580563B2 (en) 2000-12-06 2013-11-12 Anthrogenesis Corporation Placental stem cells
US20050019908A1 (en) * 2000-12-06 2005-01-27 Anthrogenesis Corporation Post-partum mammalian placenta, its use and placental stem cells therefrom
US7976836B2 (en) 2000-12-06 2011-07-12 Anthrogenesis Corporation Treatment of stroke using placental stem cells
US8057788B2 (en) 2000-12-06 2011-11-15 Anthrogenesis Corporation Placental stem cell populations
US8293223B2 (en) 2000-12-06 2012-10-23 Anthrogenesis Corporation Treatment of organ injuries and burns using placental stem cells
US8545833B2 (en) 2000-12-06 2013-10-01 Anthrogenesis Corporation Treatment of radiation injury using placental stem cells
US9149569B2 (en) 2000-12-06 2015-10-06 Anthrogenesis Corporation Treatment of diseases or disorders using placental stem cells
US20020160510A1 (en) * 2001-02-14 2002-10-31 Hariri Robert J. Renovation and repopulation of decellularized tissues and cadaveric organs by stem cells
US20080131966A1 (en) * 2001-02-14 2008-06-05 Hariri Robert J Renovation and repopulation of decellularized tissues and cadaveric organs by stem cells
US8435788B2 (en) 2001-02-14 2013-05-07 Anthrogenesis Corporation Tissue matrices comprising placental stem cells
US7311904B2 (en) 2001-02-14 2007-12-25 Anthrogenesis Corporation Tissue matrices comprising placental stem cells, and methods of making the same
US9139813B2 (en) 2001-02-14 2015-09-22 Anthrogenesis Corporation Renovation and repopulation of decellularized tissues and cadaveric organs by stem cells
US7914779B2 (en) 2001-02-14 2011-03-29 Anthrogenesis Corporation Tissue matrices comprising placental stem cells, and methods of making the same
US10351826B2 (en) 2001-09-21 2019-07-16 Garnet Biotherapeutics, Inc. Cell populations which co-express CD49c and CD90
US8753883B2 (en) 2002-02-13 2014-06-17 Anthrogenesis Corporation Treatment of psoriasis using placental stem cells
US7700090B2 (en) 2002-02-13 2010-04-20 Anthrogenesis Corporation Co-culture of placental stem cells and stem cells from a second source
US8057789B2 (en) 2002-02-13 2011-11-15 Anthrogenesis Corporation Placental stem cells derived from post-partum mammalian placenta, and uses and methods of treatment using said cells
US9694035B2 (en) 2004-03-22 2017-07-04 Mesoblast International Sarl Mesenchymal stem cells and uses therefor
EP2243826A3 (fr) * 2004-03-22 2013-11-06 Osiris Therapeutics, Inc. Cellules souches mésenchymateuses et utilisations associées
US20080095749A1 (en) * 2004-03-22 2008-04-24 Sudeepta Aggarwal Mesenchymal stem cells and uses therefor
US20100172885A1 (en) * 2004-03-22 2010-07-08 Osiris Therapeutics, Inc. Multipotent Adult Stem Cells And Uses of Multipotent Adult Stem Cells To Treat Inflammation
US11389484B2 (en) 2004-03-22 2022-07-19 Mesoblast International Sárl Mesenchymal stem cells and uses therefor
US20100330048A1 (en) * 2004-03-22 2010-12-30 Sudeepta Aggarwal Mesenchymal stem cells and uses therefor
US10960025B2 (en) 2004-03-22 2021-03-30 Mesoblast International Sárl Mesenchymal stem cells and uses therefor
US10828334B1 (en) 2004-03-22 2020-11-10 Mesoblast International Sárl Mesenchymal stem cells and uses therefor
US20110027238A1 (en) * 2004-03-22 2011-02-03 Sudeepta Aggarwal Mesenchymal Stem Cells and Uses Therefor
WO2008042174A3 (fr) * 2004-03-22 2008-06-19 Osiris Therapeutics Inc Cellules souches mésenchymateuses et leurs utilisations
US20080213227A1 (en) * 2004-03-22 2008-09-04 Sudeepta Aggarwal Mesenchymal stem cells and uses therefor
US9943547B2 (en) 2004-03-22 2018-04-17 Mesoblast International Sàrl Mesenchymal stem cells and uses therefor
US20110142807A1 (en) * 2004-03-22 2011-06-16 Pittenger Mark F Mesenchymal Stem Cells and Uses Therefor
US20090180997A1 (en) * 2004-03-22 2009-07-16 Pittenger Mark F Mesenchymal Stem Cells And Uses Therefor
US10668101B2 (en) 2004-03-22 2020-06-02 Mesoblast International Sárl Mesenchymal stem cells and uses therefor
US10729727B2 (en) 2004-03-22 2020-08-04 Mesoblast International Sárl Mesenchymal stem cells and uses therefor
US10716814B2 (en) 2004-03-22 2020-07-21 Mesoblast International Sàrl Mesenchymal stem cells and uses therefor
US20090220464A1 (en) * 2004-03-22 2009-09-03 Sudeepta Aggarwal Mesenchymal stem cells and uses therefor
US20090208463A1 (en) * 2004-03-22 2009-08-20 Pittenger Mark F Mesenchymal stem cells and uses therefor
US10548924B2 (en) 2004-08-25 2020-02-04 Tigenix, S.A.U. Use of adipose tissue-derived stromal stem cells in treating fistula
US10780132B2 (en) 2004-08-25 2020-09-22 Tigenix, S.A.U. Use of adipose tissue-derived stromal stem cells in treating fistula
US20080292600A1 (en) * 2005-06-17 2008-11-27 Song Sun Uk Treatment of graft-versus-host disease
US9439929B2 (en) * 2005-06-17 2016-09-13 Inha-Industry Partnership Institute Treatment of graft-versus-host disease
US11672831B2 (en) 2005-06-24 2023-06-13 Takeda Pharmaceutical Company Limited Use of adipose tissue-derived stromal stem cells in treating fistula
US11660318B2 (en) 2005-06-24 2023-05-30 Takeda Pharmaceutical Company Limited Use of adipose tissue-derived stromal stem cells in treating fistula
US10758575B2 (en) 2005-06-24 2020-09-01 Tigenix, S.A.U. Use of adipose tissue-derived stromal stem cells in treating fistula
US20150224146A1 (en) * 2005-09-23 2015-08-13 Tigenix, S.A.U. Cell populations having immunoregulatory activity, method for isolation and uses
US9943550B2 (en) * 2005-09-23 2018-04-17 Tigenix, S.A.U. Cell populations having immunoregulatory activity, method for isolation and uses
US9539288B2 (en) 2005-10-13 2017-01-10 Anthrogenesis Corporation Immunomodulation using placental stem cells
US8216566B2 (en) 2005-10-13 2012-07-10 Anthrogenesis Corporation Treatment of multiple sclerosis using placental stem cells
US8895256B2 (en) 2005-10-13 2014-11-25 Anthrogenesis Corporation Immunomodulation using placental stem cells
US7682803B2 (en) 2005-10-13 2010-03-23 Anthrogenesis Corporation Immunomodulation using placental stem cells
US9078898B2 (en) 2005-12-29 2015-07-14 Anthrogenesis Corporation Placental stem cell populations
US10383897B2 (en) 2005-12-29 2019-08-20 Celularity, Inc. Placental stem cell populations
US8202703B2 (en) 2005-12-29 2012-06-19 Anthrogenesis Corporation Placental stem cell populations
US8455250B2 (en) 2005-12-29 2013-06-04 Anthrogenesis Corporation Co-culture of placental stem cells and stem cells from a second source
US8591883B2 (en) 2005-12-29 2013-11-26 Anthrogenesis Corporation Placental stem cell populations
US8691217B2 (en) 2005-12-29 2014-04-08 Anthrogenesis Corporation Placental stem cell populations
US20140248244A1 (en) * 2006-01-13 2014-09-04 Mesoblast International Sarl Mesenchymal Stem Cells Expressing TNF-alpha Receptors
US11821004B2 (en) 2006-01-13 2023-11-21 Mesoblast International Sárl Mesenchymal stem cells expressing TNF-α receptors
US9498497B2 (en) * 2006-02-01 2016-11-22 Medipost Co., Ltd. Method of treating lung diseases using cells separated or proliferated from umbilical cord blood
US20080311088A1 (en) * 2006-02-01 2008-12-18 Samsungn Life Public Welfare Foundation Method of Treating Lung Diseases Using Cells Separated Or Proliferated From Umbilical Cord Blood
US20070207130A1 (en) * 2006-03-01 2007-09-06 Calvin Cao Stem cell therapy to treat symptoms of avian flu and other diseases
US20100008992A1 (en) * 2006-05-19 2010-01-14 Medistem Laboratories, Inc. Treatment of disc degenerative disease and compositions for same
US9598673B2 (en) * 2006-05-19 2017-03-21 Creative Medical Health Treatment of disc degenerative disease
US7993918B2 (en) 2006-08-04 2011-08-09 Anthrogenesis Corporation Tumor suppression using placental stem cells
US20080159995A1 (en) * 2006-10-03 2008-07-03 Monica Silverstone Spiteri Treatment of fibrosis
US8916146B2 (en) 2007-02-12 2014-12-23 Anthrogenesis Corporation Treatment of inflammatory diseases using placental stem cells
US8460650B2 (en) 2007-02-12 2013-06-11 Anthrogenesis Corporation Treatment of inflammatory diseases using placental stem cells
US10624952B2 (en) 2007-03-27 2020-04-21 Cardiovascular Biotherapeutics, Inc. Systems and methods for angiogenic treatment in wound healing
US11224635B2 (en) * 2007-03-27 2022-01-18 Venturis Thereuptics, Inc. Therapeutic angiogenesis for treatment of the spine and other tissues
US20130230454A1 (en) * 2007-03-27 2013-09-05 Cardiovascular Biotherapeutics, Inc. Therapeutic Angiogenesis for Treatment of the Spine and Other Tissues
US20160263162A1 (en) * 2007-04-06 2016-09-15 Xon Cells, Inc. Stem cell therapy for the treatment of autism and other disorders
US20080260703A1 (en) * 2007-04-23 2008-10-23 Medistem Labortories Treatment of Insulin Resistance and Diabetes
US20120148544A1 (en) * 2007-06-15 2012-06-14 Garnet Biotherapeutics, Inc. Treatment of Diseases and Disorders Using Self-Renewing Colony Forming Cells Cultured and Expanded In Vitro
US20110262402A1 (en) * 2007-09-07 2011-10-27 Masahiko Kuroda Therapeutic and prophylactic agents for arthritis
US20100189750A1 (en) * 2007-09-12 2010-07-29 Yeda Research And Development Co. Ltd. Methods of treating tumors in immune-privileged sites
US8741315B2 (en) * 2007-09-12 2014-06-03 Yeda Research And Development Co. Ltd. Methods of treating tumors in immune-privileged sites
US9517248B2 (en) 2007-09-19 2016-12-13 Pluristem Ltd. Adherent cells from adipose or placenta tissues and use thereof in therapy
US20110104100A1 (en) * 2007-10-04 2011-05-05 Medistem Laboratories, Inc. Compositions and methods of stem cell therapy for autism
US20110020291A1 (en) * 2007-11-17 2011-01-27 Debrabrata Banerjee Use of stem cells for wound healing
US20110044958A1 (en) * 2008-03-14 2011-02-24 The Board Of Trustees Of The University Of Illinois Activated mesenchymal stem cells for the prevention and repair of inflammatory states
WO2009114860A3 (fr) * 2008-03-14 2010-01-07 The Board Of Trustees Of The University Of Illinois Cellules souches mésenchymateuses activées pour la prévention et la réparation d’états inflammatoires
WO2009114860A2 (fr) * 2008-03-14 2009-09-17 The Board Of Trustees Of The University Of Illinois Cellules souches mésenchymateuses activées pour la prévention et la réparation d’états inflammatoires
US9011840B2 (en) 2008-03-14 2015-04-21 The Board Of Trustees Of The University Of Illinois Activated mesenchymal stem cells for wound healing and impaired tissue regeneration
KR20170098933A (ko) * 2008-08-04 2017-08-30 타이제닉스, 에스.에이.유. 중간엽 줄기 세포의 용도
KR101764643B1 (ko) * 2008-08-04 2017-09-05 타이제닉스, 에스.에이.유. 중간엽 줄기 세포의 용도
US20120027730A1 (en) * 2008-08-04 2012-02-02 Consejo Superior De Investigaciones Cientificas Uses of mesenchymal stem cells
KR101974842B1 (ko) * 2008-08-04 2019-05-03 타이제닉스, 에스.에이.유. 중간엽 줄기 세포의 용도
US10104880B2 (en) 2008-08-20 2018-10-23 Celularity, Inc. Cell composition and methods of making the same
US8828376B2 (en) 2008-08-20 2014-09-09 Anthrogenesis Corporation Treatment of stroke using isolated placental cells
US8728805B2 (en) 2008-08-22 2014-05-20 Anthrogenesis Corporation Methods and compositions for treatment of bone defects with placental cell populations
US10238692B2 (en) * 2008-11-14 2019-03-26 Medipost Co., Ltd Composition comprising a culture solution of mesenchymal stem cells for the treatment of neural diseases
US20110262393A1 (en) * 2008-11-14 2011-10-27 Medipost Co., Ltd. Composition comprising mesenchymal stem cells or culture solution of mesenchymal stem cells for the prevention or treatment of neural diseases
US9198938B2 (en) 2008-11-19 2015-12-01 Antrhogenesis Corporation Amnion derived adherent cells
US8367409B2 (en) 2008-11-19 2013-02-05 Anthrogenesis Corporation Amnion derived adherent cells
US20110283371A1 (en) * 2008-12-09 2011-11-17 University Of Southern California Stem Cell Modified Animal Model for Aging-Related Degenerations, Stem Cell Based Methods and Compositions for Extending Lifespan and Treating SLE-Like Autoimmune Diseases
US10098333B2 (en) * 2008-12-09 2018-10-16 University Of Southern California Method for treating an SLE-like autoimmune disease in a human subject consisting of administering stem cells from human exfoliated deciduous teeth (SHED) and erythropoietin (EPO) to said human subject
US20110020293A1 (en) * 2009-07-21 2011-01-27 Abt Holding Company Use of Stem Cells to Reduce Leukocyte Extravasation
US9121007B2 (en) 2010-01-26 2015-09-01 Anthrogenesis Corporatin Treatment of bone-related cancers using placental stem cells
US9254302B2 (en) 2010-04-07 2016-02-09 Anthrogenesis Corporation Angiogenesis using placental stem cells
US8562973B2 (en) 2010-04-08 2013-10-22 Anthrogenesis Corporation Treatment of sarcoidosis using placental stem cells
US9937208B2 (en) 2010-05-12 2018-04-10 Abt Holding Company Modulation of splenocytes in cell therapy
US10758570B2 (en) 2010-05-12 2020-09-01 Abt Holding Company Modulation of splenocytes in cell therapy
US10668102B2 (en) 2010-06-02 2020-06-02 Rutgers, The State University Of New Jersey Lineage differentiation of encapsulated embryonic stem cells
US20120020931A1 (en) * 2010-06-02 2012-01-26 Rutgers, The State University Of New Jersey Therapeutic encapsulated embryonic stem cells and mesenchymal stromal cells
US8969315B2 (en) 2010-12-31 2015-03-03 Anthrogenesis Corporation Enhancement of placental stem cell potency using modulatory RNA molecules
US20120288480A1 (en) * 2011-02-22 2012-11-15 Taipei Medical University Cell population comprising orbital fat-derived stem cells (ofscs) and their isolation and applications
US9040035B2 (en) 2011-06-01 2015-05-26 Anthrogenesis Corporation Treatment of pain using placental stem cells
US11090339B2 (en) 2011-06-01 2021-08-17 Celularity Inc. Treatment of pain using placental stem cells
US9925221B2 (en) 2011-09-09 2018-03-27 Celularity, Inc. Treatment of amyotrophic lateral sclerosis using placental stem cells
US10272118B2 (en) 2013-02-12 2019-04-30 Replicel Life Sciences Inc. Compositions and methods for treating and repairing tendons
US11071752B2 (en) 2013-04-12 2021-07-27 Abt Holding Company Organs for transplantation
US9861660B2 (en) 2013-04-12 2018-01-09 Saverio LaFrancesca Organs for transplantation
US10071119B2 (en) * 2013-05-08 2018-09-11 Shanghai Institutes For Biological Sciences, Chinese Academy Of Sciences Application of mesenchymal stem cells in prophylaxis or treatment of stress response-induced weakened immunity
US20160120908A1 (en) * 2013-05-08 2016-05-05 Shanghai Institutes For Biological Sciences, Chinese Academy Of Sciences Application of mesenchymal stem cells in prophylaxis or treatment of stress response-induced weakened immunity
US10500233B2 (en) 2014-02-12 2019-12-10 Replicel Life Sciences Inc. Compositions and methods for treating bone, joints and cartilage
US9518251B2 (en) 2014-09-17 2016-12-13 Gwo Xi Stem Cell Applied Technology Co., Ltd. Method for enhancing therapeutic effect of stem cells on autoimmune diseases, cardiovascular diseases, and/or hematological diseases
US9523081B2 (en) * 2014-09-17 2016-12-20 Gwo Xi Stem Cell Applied Technology Co., Ltd. Method for enhancing therapeutic effect of stem cells on autoimmune diseases, cardiovascular diseases, and/or hematological diseases
US11273182B2 (en) 2016-03-14 2022-03-15 Takeda Pharmaceutical Company Limited Adipose tissue-derived stromal stem cells for use in treating refractory complex perianal fistulas in Crohn's disease
US10357518B2 (en) 2016-03-14 2019-07-23 Tigenix S.A.U. Adipose tissue-derived stromal stem cells for use in treating refractory complex perianal fistulas in Crohn's disease
US10980858B2 (en) 2016-06-20 2021-04-20 Fujifilm Corporation Trophic factor releasing agent and inflammatory disease treating agent
US10987381B2 (en) * 2017-01-27 2021-04-27 Neil Riordan Mesenchymal stem cells with enhanced efficacy in treatment of autoimmunity particularly rheumatoid arthritis
US20180214489A1 (en) * 2017-01-27 2018-08-02 Neil Riordan Mesenchymal stem cells with enhanced efficacy in treatment of autoimmunity particularly rheumatoid arthritis
US20210386833A1 (en) * 2018-10-04 2021-12-16 National Institute For Materials Science Angiogenesis promoter and therapeutic method
CN113396333A (zh) * 2019-01-31 2021-09-14 普里梅真生物技术有限责任公司 使用间充质干细胞和免疫调节治疗特应性皮炎

Also Published As

Publication number Publication date
EP3461884A1 (fr) 2019-04-03
KR20090065478A (ko) 2009-06-22
WO2008042174A2 (fr) 2008-04-10
EP2298861B1 (fr) 2017-09-13
CA2564679A1 (fr) 2005-10-06
US20090208463A1 (en) 2009-08-20
EP2824175A2 (fr) 2015-01-14
EP2824175A3 (fr) 2015-05-06
WO2005093044A1 (fr) 2005-10-06
US9943547B2 (en) 2018-04-17
US20140161776A1 (en) 2014-06-12
US10729727B2 (en) 2020-08-04
US20200246387A1 (en) 2020-08-06
JP2007530543A (ja) 2007-11-01
AU2009200019A1 (en) 2009-02-05
EP1974016A4 (fr) 2009-04-01
JP2010505764A (ja) 2010-02-25
US9694035B2 (en) 2017-07-04
US10716814B2 (en) 2020-07-21
US20150272997A1 (en) 2015-10-01
EP1727892B1 (fr) 2012-05-02
US11389484B2 (en) 2022-07-19
EP2298862A3 (fr) 2011-08-24
EP1974016A2 (fr) 2008-10-01
EP2298862B1 (fr) 2017-08-30
CA2659825A1 (fr) 2008-04-12
EP2298861A2 (fr) 2011-03-23
US20230076630A1 (en) 2023-03-09
US20140154276A1 (en) 2014-06-05
EP2298864B1 (fr) 2017-10-11
US10668101B2 (en) 2020-06-02
EP2298862A2 (fr) 2011-03-23
US20100172885A1 (en) 2010-07-08
US10828334B1 (en) 2020-11-10
EP2243826A2 (fr) 2010-10-27
WO2008042174A3 (fr) 2008-06-19
US20110318315A1 (en) 2011-12-29
CN101384702A (zh) 2009-03-11
EP2298863A3 (fr) 2011-04-13
AU2009200019B2 (en) 2012-08-02
US20140328807A1 (en) 2014-11-06
US20080213227A1 (en) 2008-09-04
US20150017132A1 (en) 2015-01-15
EP2298864A2 (fr) 2011-03-23
US20110027238A1 (en) 2011-02-03
EP1727892A4 (fr) 2007-08-22
EP2824174B1 (fr) 2018-11-28
US20200360442A1 (en) 2020-11-19
EP2824175B1 (fr) 2017-11-29
AU2005227295A1 (en) 2005-10-06
US20110318314A1 (en) 2011-12-29
EP2824175B2 (fr) 2020-10-28
US20090180997A1 (en) 2009-07-16
EP2298863B1 (fr) 2015-07-22
US20110142807A1 (en) 2011-06-16
EP2243826A3 (fr) 2013-11-06
EP2298861A3 (fr) 2011-11-30
EP2298864A3 (fr) 2011-11-23
US20110311496A1 (en) 2011-12-22
EP1727892A1 (fr) 2006-12-06
US20190201447A1 (en) 2019-07-04
AU2010200916A1 (en) 2010-04-01
EP2824174A1 (fr) 2015-01-14
US20190240259A1 (en) 2019-08-08
US10960025B2 (en) 2021-03-30
EP2298863A2 (fr) 2011-03-23
US20190175657A1 (en) 2019-06-13
CA2564679C (fr) 2015-06-23

Similar Documents

Publication Publication Date Title
US10828334B1 (en) Mesenchymal stem cells and uses therefor
CA2868733A1 (fr) Cellules souches mesenchymateuses destinees au traitement de l'inflammation
AU2017268656B2 (en) Mesenchymal stem cells and uses therefor

Legal Events

Date Code Title Description
AS Assignment

Owner name: OSINIS THERAPEUTICS, INC., MARYLAND

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:PITTENGER, MARK F.;AGGARWAL, SUDEEPTA;REEL/FRAME:016171/0133;SIGNING DATES FROM 20050414 TO 20050418

AS Assignment

Owner name: NAVY, UNITED STATES OF AMERICA, THE, AS REPRESENTE

Free format text: CONFIRMATORY LICENSE;ASSIGNOR:OSIRIS THERAPEUTICS, INC.;REEL/FRAME:017822/0527

Effective date: 20060303

AS Assignment

Owner name: NAVY, SECRETARY OF THE UNITED STATES, VIRGINIA

Free format text: CONFIRMATORY LICENSE;ASSIGNOR:OSIRIS THERAPEUTICS, INC.;REEL/FRAME:018163/0186

Effective date: 20060303

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: MESOBLAST INTERNATIONAL S?RL, SWITZERLAND

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:OSIRIS THERAPEUTICS, INC.;REEL/FRAME:031533/0828

Effective date: 20131010

Owner name: MESOBLAST INTERNATIONAL SARL, SWITZERLAND

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:OSIRIS THERAPEUTICS, INC.;REEL/FRAME:031533/0828

Effective date: 20131010